Lycoming County was formed from Northumberland County on 13 April 1795. At the time it was formed the county was much larger than it is today. It took up most of the land that is now north central Pennsylvania. The following counties have been formed from land that was once part of Lycoming County: Armstrong, Bradford, Centre, Clearfield, Clinton, Indiana, Jefferson, McKean, Potter, Sullivan, Tioga, Venango, Warren, Forest, Elk and Cameron. Lycoming County was originally named Jefferson County in honor of Thomas Jefferson. This name proved to be unsatisfactory. The name change went through several steps. First a change to Lycoming County was rejected, next the name Susquehanna County was struck down as was Muncy County, before the legislature revisited and settled on Lycoming County for Lycoming Creek the stream that was the center of the pre-Revolutionary border dispute.

The first recorded inhabitants of Lycoming County were the Iroquoian speaking Susquehannocks. Their name meant "people of the muddy river" in Algonquin. Decimated by diseases and warfare, they had died out, moved away, or been assimilated into other tribes by the early 18th century. The lands of the West Branch Susquehanna River Valley were then chiefly occupied by the Munsee phratry of the Lenape (or Delaware), and were under the nominal control of the Five (later Six) Nations of the Iroquois.

Madame Montour's village of Otstonwakin or Ostuagy was a vitally important location during the settlement of what is now Lycoming County. Her village at the mouth of Loyalsock Creek on the West Branch Susquehanna River was an important stopping point for the Moravian missionaries who were spreading the gospel throughout the wilderness of Pennsylvania during the 1740s. Count Zinzendorf, a missionary being guided by Conrad Weiser with the permission of Shikellamy came to Ostuagy in 1742.

Madame Montour was known to be a friend of the British. She welcomed the white men who were beginning to migrate into the West Branch Susquehanna River Valley. She also had a great amount of influence with the various Indian tribes they were feeling the pressure of colonial expansion. Madame Montour remained loyal to the British despite several attempts by the French to bring her over to their side. Historians note that this was remarkable due to the fact the that British colonial government sometimes went as long as a year without paying her for her services.

Elizabeth Catherine Montour was the mother of three children. A son, Louis, served as a translator during the French and Indian War. He was killed during the war. Her daughter, Margaret, later to be known as "French Margaret" went on to become the leader of "French Margaret's Town" an Indian settlement at the mouth of Lycoming Creek just a few miles up the West Branch Susquehanna River from Madame Montour's village. Her son, Andrew took over leadership of Otstonwakin upon her death in the late 1740s. Andrew inherited his mother’s gift for languages. He spoke French, English, Lenape, Shawnee and the Iroquoian languages. Comfortable with both Native Americans and Europeans, he made a good living as a translator for both settlers and local tribes. In 1742 when Count Zinzendorf met Montour he wrote that Montour looked "decidedly European, and had his face not been encircled with a broad band of paint we would have thought he was one." He also served as a translator with Conrad Weiser and Chief Shikellamy. He was granted 880 acres (3.6 km²) of land by the Province of Pennsylvania in the Montoursville area. He later was appointed as a captain in George Washington's Army at Fort Necessity during the French and Indian War. Andrew Montour left Montoursville at some point and moved to Juniata County before finally settling on Mountour's Island in the Allegheny River near Pittsburgh.

In the American Revolutionary War, settlements throughout the Susquehanna valley were attacked by Loyalists and Native Americans allied with the British. After the Wyoming Valley battle and massacre in the summer of 1778 (near what is now Wilkes-Barre) and smaller local attacks, the "Big Runaway" occurred throughout the West Branch Susquehanna valley. Settlers fled feared and actual attacks by the British and their allies. Homes and fields were abandoned, with livestock driven along and a few possessions floated on rafts on the river east to Muncy, then further south to Sunbury. The abandoned property was burnt by the attackers. Some settlers soon returned, only to flee again in the summer of 1779 in the "Little Runaway." Sullivan's Expedition helped stabilize the area and encouraged resettlement, which continued after the war.

The Fair Play Men were illegal settlers (squatters) who established their own system of self-rule from 1773 to 1785 in the West Branch Susquehanna River valley of Pennsylvania in what is now the United States. Because they settled in territory claimed by Native Americans, they had no recourse to the Pennsylvania colonial government. Accordingly they established what was known as the "Fair Play System," with three elected commissioners who ruled on land claims and other issues for the group. In a remarkable coincidence, the Fair Play Men made their own Declaration of Independence from Britain on July 4, 1776 beneath the "Tiadaghton Elm" on the banks of Pine Creek.

Fort Antes was a stockade surrounding the home of Colonel John Henry Antes, built circa 1778 in Revolutionary Pennsylvania. The fort was built under the direction of Colonel Antes, who was a member of the Pennsylvania militia. It was on the east side of Antes Creek, overlooking and on the left bank of the West Branch Susquehanna River on a plateau in Nippenose Township south of modern day Jersey Shore in western Lycoming County. The local militia held the fort for a short period of time until it was ordered to abandon Fort Antes during the Big Runaway by Colonel Samuel Hunter. Despite being abandoned and attempts by the attacking British forces to burn it down, Fort Antes was one of only two structures in the valley to survive the Big Runaway.

Lycoming Creek and the Sheshequin Path played an important role in the early history of Lycoming County. The path was a major Native American trail in that ran between two Native American villages: "French Margaret's Town" on the West Branch Susquehanna River (part of modern day Williamsport in Lycoming County) and "Sheshequin" on the North Branch of the Susquehanna River (modern day Ulster Township, in Bradford County). The path ran north and east along Lycoming Creek in Lycoming County and followed much of Towanda Creek in Bradford County. It was a shortcut between the two main branches of the Susquehanna River and was used by early settlers as well as Native Americans.

Lycoming Creek which begins in McNett Township also served as a highway of sorts during the colonial era of Pennsylvania's history. The stream was used by early explorers and the Native Americans in the area as a means of travel. They were able to float their canoes down the creek and into the West Branch Susquehanna River. This mode of transportation was considerably faster than walking the path. Conrad Weiser guided Moravian missionaries along the creek and path to reach Onondaga the capital of the Iroquois Confederacy in 1737. Raiding parties of Indian warriors used the creek and path in 1770 when conducting attacks on the West Branch Susquehanna Valley strongholds of Fort Muncy and Fort Freeland. Colonel Thomas Hartley led the 6th Pennsylvania Regiment up the Sheshequin Path during the American Revolution. Hartley's expedition in 1778 preceded the Sullivan Expedition of 1779. Both Hartley and Sullivan were instrumental in claiming the frontier of Pennsylvania and New York for the forces of the Continental Army. As Hartley and his men passed through Lewis Township the Sheshequin path was widened. The widening of the path helped to open this area to settlement in the years following the Revolution.

1615 - The first European in Lycoming County was Etienne Brule. He was an voyageur for New France. Brule descended the West Branch Susquehanna River and was held captive by a local Indian tribe near what is now Muncy before escaping and returning to Canada.

1761 - The first permanent homes were built in Muncy. Three log cabins were built by Bowyer Brooks, Robert Roberts and James Alexander.

1772 - The first gristmill is built on Muncy Creek by John Alward.

1775 - The first public road is built along the West Branch Susquehanna River. The road followed Indian trails from Fort Augusta in what is now Sunbury to Bald Eagle Creek near modern day Lock Haven.

1786 - The first church built in the county was Lycoming Presbyterian church in what was known as Jaysburg and is now the Newberry section of Williamsport.

1792 - The first sawmill was built on Lycoming Creek by Roland Hall.

1795 - The first elections for Lycoming County government are held soon after the county was formed from Northumberland County. The elected officers were Samuel Stewart, county sheriff and the first county commissioners were John Hanna, Thomas Forster and James Crawford. Andrew Gregg was elected to represent Lycoming County in the United States Congress, William Hepburn was voted to the Pennsylvania State Senate and Flavel Roan, Hugh White and Robert Martin served as representatives in the Pennsylvania General Assembly.

1823 - The county government funded the construction of the first bridges over Loyalsock and Lycoming Creeks.

1839 - The first railroad is built. It connected Williamsport with Ralston in northern Lycoming County. The railroad followed Lycoming Creek.

The founding fathers of Williamsport and to an extent Lycoming County were Michael Ross and William Hepburn. Both men played a great role in the formation of Lycoming County and the establishment of Williamsport as the county seat.

Michael Ross was born in Scotland on 12 July 1759. He and his mother migrated across the Atlantic Ocean in 1772 and landed in Philadelphia, Pennsylvania. They became indentured servants to Samuel Wallis, known as the "Land King" of the West Branch Susquehanna River Valley. Wallis had extensive holdings in Muncy Township. Wallis brought Michael Ross and his mother to Muncy Township where Ross was trained as a surveyor's assistant. Michael Ross must have made a good impression upon Wallis, since Wallis gave Ross 109 acres (0.4 km²) of land and a favorable letter of recommendation. Ross quickly became a successful surveyor and farmer. He was able to use his profits to purchase 285 acres (1.2 km²) of land along the West Branch Susquehanna River, between Loyalsock and Lycoming Creeks. This land originally called "Virginia" was to in time become Williamsport, the county seat of Lycoming County.

William Hepburn was born in County Donegal, Ireland in 1753. He migrated to the Thirteen Colonies in 1773 or 1774. Hepburn lived in the Sunbury area for a short time before moving up the West Branch Susquehanna River to what is now Duboistown where he worked for Andrew Culbertson in digging the race for Culberton's Mill. Hepburn also joined the local militia. During the American Revolution, the West Branch Valley came under attack from Loyalist and Indian forces. These attacks were known as the Big Runaway in 1778 and the later Little Runaway in 1779. Hepburn rose to the position of colonel and was the commanding officer at Fort Muncy, Samuel Wallis' fortified home in Muncy Township. Hepburn, reportedly, gave the orders to Robert Covenhoven and Rachel Silverthorn to spread the word of the impending attacks. Following the Big Runaway, Hepburn kept a permanent connection with the Covenhoven family by marrying, Crecy Covenhoven, the sister of Robert. Hepburn also bought 300 acres (1.2 km²) of land, to the west of Ross' holdings. His land, known as "Deer Park," combined with Ross' "Virginia" would eventually become Williamsport.

The selection of Williamsport as county seat was a major controversy in the early history of Lycoming County. It involved a bitter rivalry between an old frontier town and an upstart town that was built on a swamp. The first commissioners and officers of Lycoming County had their first offices and held their first court in Jaysburg (now part of the Newberry section of Williamsport). Jaysburg was on the western side of Lycoming Creek on a high piece of land. The land to the east of Lycoming Creek was known as "Deer Park" and was quite swampy. Jaysburg was at the time the only sizeable village west of Muncy. Although Muncy was and still is in Lycoming County it was not considered as an option for county seathood, possibly due to its proximity to the southern and eastern borders of the county. Jaysburg's buildings were sufficient enough to serve as the first courthouse and jail in the history of Lycoming County. It seemed to be the most logical place for establishing a county seat and many of its residents quite sure that their town would indeed be the county seat. This was not to be. The county seat was awarded to a new community across the creek and Jaysburg soon disappeared from the map and its land was absorbed by the new city of Williamsport.

One of the first county judges, William Hepburn, owned the land on the opposite shore of Jaysburg that was known as Deer Park. Another land speculator, Michael Ross owned 285 acres (1.2 km²) of land in what is now the central part of Williamsport. Ross had laid out a town on his property and a few homes were being built. Ross and Hepburn would team together to create Williamsport from land that was swampy and thought to be uninhabitable by the Susquehannocks who had originally inhabited the West Branch Susquehanna River Valley. Ross wanted to sell his properties and rightly believed that they would quickly sell if his town was made county seat. Hepburn desired for political power, had little money by which to gain that power, but had a lot of land, land that could also be sold if Williamsport were to become the county seat.

The citizens of Jaysburg saw the attempts by Hepburn and Ross as a threat and they fought back. They believed that Jaysburg was much better suited to be the seat of government. It was already well established and held the higher and drier land. They firmly believed that Williamsport would be frequently flooded and that the swamps would carry deadly diseases. The Jaysburgers sought to prove their point by sending an affidavit to the state capital stating that the land was prone to flooding and thereby unsuitable to be the county seat. A resident of Northumberland wrote a sworn affidavit that he had once "tied up" his boat on a point of land on what is now East Third and State Streets in downtown Williamsport. He accessed it by way of a "gut" or an arm of the river that backflowed into the land. The affidavit was the proof that the Jaysburg interests needed to discredit Williamsport as a possible location for the county seat. Hepburn and Ross heard of this potentially financially devastating document and sought to have it destroyed before it reached the state government. It is supposed that men working for Hepburn and Ross met up with the messenger bearing the affidavit at the Russell Inn on the corner of East Third and Mulberry Streets in Williamsport and got him intoxicated. Then they are said to have cut open his saddle bags and made off with the documents.

The state commissioners by this time had begun to grow very weary of the rivalry between Jaysburg and Williamsport. They began to consider a third possibility for the county seat, a new village that was further up the West Branch Susquehanna River west of the mouth of Pine Creek in what is now Clinton County. The town of Dunnsburg even went as far as offering, free of charge, lots on which to build the buildings that would be required by the county government. It appeared as if the state commissioners would choose neither Williamsport nor Jaysburg, instead choosing the outpost of Dunnsburg. This is when Judge Hepburn and Michael Ross set out their plan that ultimately lead towards Williamsport being named the county seat.

Hepburn convinced Ross to offer lots of his property to the state commissioners for the building of a county courthouse and jail. This he believed would induce the state commissioners to give the seathood to Williamsport. Ross is stated to have had little interest in politics, but being a good businessman was interested in selling his land. Ross agreed to Hepburn's suggestion and the lots were offered to the state commission. The state commission accepted the lots and Williamsport was finally named the county seat of Lycoming County.

When Williamsport was established as the county seat it was little more than a few cabins spread here and there in the aforementioned swampy areas. Jaysburg served as the defacto county seat for several years after Williamsport was "officially" named the seat of government for Lycoming County. This delay became a cause for concern to the residents of county and the state government in Philadelphia. The county commissioners delayed in constructing a courthouse and jail in Williamsport until 1799. The jail was finally opened in 1801. Next the commissioners approved the construction of the county courthouse in Williamsport. Construction also began in 1800 and work was completed in late 1804, nearly ten years after Williamsport was named the county seat.

The Susquehanna Boom was a system of cribs in the West Branch Susquehanna River designed to hold timber in the river until it could be processed at one of the nearly 60 sawmills along the West Branch Susquehanna River between Lycoming and Loyalsock Creeks in Lycoming County, Pennsylvania. The boom was constructed in 1846 under the supervision of James H. Perkins. A boom is a chain or line of connected floating timbers extended across a river, lake, or harbor (as to obstruct passage or catch floating objects). The Susquehanna Boom extended seven miles upstream from Duboistown to the village of Linden in Woodward Township. The boom was constructed by creating a series of man-made islands known as "cribs." These cribs built of local mountain stone and sunken timber were stretched diagonally across the river, beginning on the south side near Duboistown and ending on the north side near Linden. The boom was made of 352 separate cribs that were 22 feet (7 m) high. The boom was opened and closed at the upper end by a device known as a "sheer boom." It was 1,000 feet (300 m) long and was controlled with a hand-powered windlass. The sheer boom gathered the logs into the main boom that was capable of holding up to 300 million board feet (700,000 m³) of logs. The lower end of the boom was where the logs were sorted. The mills in Williamsport, South Williamsport, and Duboistown each had their own distinctive brand burnt into the logs. The men working at the end of the boom would sort the logs according to their corresponding brand and float them into the correct holding pond along the bank of the river. During the height of the lumber industry in Lycoming County, 1861-1891, the various mills produced 5.5 billion board feet (13 million m³) of lumber. Williamsport became one of the most prosperous cities in Pennsylvania and in the United States. Men like James H. Perkins, Peter Herdic, and Mahlon Fisher became millionaires while many of the men who actually worked in the river struggled to survive on the wages paid to them by the lumber barons.

The Muncy Abolition Riot of 1842 occurred in April 1842 in Muncy. The riot led to the conviction and ultimate pardoning of 13 men from who rioted at a schoolhouse where a now unknown abolitionist speaker who was invited by some local Quakers spoke against slavery.

One of the common misconceptions about United States history prior to the Civil War is that all the citizens of the northern states were against slavery. In fact many of the "Yankees," were all for slavery, especially in states closer to the Confederacy like Pennsylvania, Ohio and Delaware. There were more than a few abolitionists in Pennsylvania and Enos Hawley, a Quaker citizen of Muncy was one of the most prominent abolitionists in Lycoming County. Hawley, a tanner by trade, was like most Quakers a strong supporter of the abolition of slavery. Hawley invited, a now unknown, speaker to come to Muncy to speak against slavery. This speaker arrived in April 1842. His arrival and coinciding speech set off a tremendous riot that lead to the near destruction of a local schoolhouse and the controversial pardoning of the rioters by Pennsylvania Governor David R. Porter.

The anti-slavery speaker gave his speech at a one room school in Muncy in April 1842. During the course of the speech eighteen men gathered outside the schoolhouse. They began throwing rocks and other debris at the school, breaking all of the windows. Enos Hawley and the guest speaker were both injured in the assault. Upon fleeing the school the abolitionists were pelted with eggs. The rioters followed Hawley and his guest to Hawley's home at the corner of High and Main Streets. They continued the assault on Hawley's home until after midnight when the local law enforcement officers were able to quell the riot and arrest the rioters. The rioters were indicted in September and went to trial in October when thirteen of the eighteen rioters were found guilty as charged. The jury's deliberation was quite a long process.

Abraham Updegraff was a member of the jury who was the driving force that led to the conviction of the rioters. Updegraff, an ardent abolitionist who was a vital member of the Underground Railroad in Lycoming County, was able to convince his peers that the rioters deserved to be punished. The first jury vote was 11 to 1 in favor of acquittal, with Upedgraff being the lone dissenter. Updegraff argued that "we have been sworn to try this case according to the law and the evidence presented and that if no contradictory evidence offered by the defendants than we could do nothing more than to convict them." He was able to make his argument in German which was the native tongue of three other jurors. The second voted was 9 to 3 in favor of acquittal. A third vote brought about the conviction of 13 of the 18 men charged in the Muncy Abolition Riot of 1842. This conviction was essentially overturned by Governor David R. Porter when he pardoned the rioters several days later. Governor Porter's statement of pardon said, "It is represented to me by highly respected citizens of Lycoming County, that this prosecution was instituted more with a view to the accomplishment of political ends than to serve the cause of law and order."

Porter's pardon message placed the blame for the riot on the abolitionist speaker. Porter stated that the speech was "notoriously offensive to the minds of those to whom they were addressed and were calculated to bring about a breach of the peace." This pardon led to Governor Porter being given the less than flattering nickname of the "Previous Pardonin Porter." Historians believe that Porter pardoned the rioters under political pressure that was rampant, in the years prior to the Civil War, regarding the issue of slavery.

Daniel Hughes was a conductor in the Underground Railroad based in Loyalsock Township and Williamsport. He was the owner of a barge on the Pennsylvania Canal and transported lumber from Williamsport on the West Branch Susquehanna River to Havre de Grace, Maryland. Hughes hid runaway slaves in the hold of his barge on his return trip up the Susquehanna River to Lycoming County where he provided shelter on his property near the Loyalsock Township border with Williamsport before moving further north and to eventual freedom in Canada. Hughes' home was located in a hollow or small valley in the mountains just north of Williamsport. This hollow is now known as Freedom Road having previously been called Nigger Hollow. In response to the actions of concerned African American citizens of Williamsport, the pejorative name was formally changed by the Williamsport City Council in 1936.

Soon after the beginning of the American Civil War, United States President Abraham Lincoln called for the northern states to muster 75,000 soldiers. Patriotic fever swept through Lycoming County as the people of the north anticipated what they believed would be a rapid defeat of the rebellious Confederate States of America. Twelve days after Fort Sumter was fired up, Lycoming County was able to produce three companies of soldiers that totalled 244 men.

The three companies departed from the railroad station near the corner of what is now Pine Street and Little League Boulevard. On that day all businesses in Williamsport closed until the trains pulled away. Two civic bands played at the send-off. The trained left the station at 8:30 amid loud cheers and celebration.

The citizens of Lycoming County continued to support the war in various ways as numerous trains passed through Williamsport from points north and west carrying new troops to the battles in the south. Ladies groups set up tables at the Northern Central Railway depot. Here they were able to feed and encourage the passing soldiers. The tables were heaped with various foods and drinks including cold meat, bread, fresh vegetables, buttermilk, lager beer and a variety distilled spirits. Ladies Aid Societies banded together to roll bandages and knit socks, trousers, and shirts for the soldiers.

The exact numbers of soldiers from Lycoming County to serve during the Civil War is unknown. What is known is that 2,481 men from Lycoming County served in the war from May 12, 1863 until April 14, 1865. This count was conducted by the local Congressional District. The landlords and employers of Lycoming County routinely froze rent payments and held the jobs of the departed soldiers. The Lycoming Gazette reported, "Whenever a man quits an employment to go into his countries service his employer will religiously hold the same place open for him until he comes home again."