The area that is now the town of Lisle was first settled around 1791. The town was formed from the town of Union in 1801. Later, parts of Lisle were used to form new towns in the county: in 1831, a division of Lisle into four parts created three new towns: Barker, Nanticoke, and Triangle.
John D. Rockefeller's birthplace is located northeast of Lisle by a few miles, and his relatives lived in Lisle. Rockefeller's father lived outside the morals of the Lisle community since he had two wives. Rockefeller said about the area, "I hazard to think what might have become of me had I not left."
One reported original settlement, the Torry Lot, was located approximately within a one mile radius of the hill on Hotaling's property (the first owner of a piece of the Boston Purchase). There apparently were some disputes with the local Indians, and Hotaling's son was killed by Indians. The original "Torry Lot" settlers burned their possessions and moved because their livestock died, and they deemed the area uninhabitable.
The first white settlers around 1791 included Josiah Patterson, Ebenezer Tracy, Edward Edwards, David Manning, Eliphalet Parsons and Whittlesey Gleason. By 1830, Lisle was "congested" and had a population of 4,393 - more than any other town in Broome County. Lisle was a shopping mecca, and the wares produced at the numerous mills were being sold in the thriving "Center Lisle" (originally called Yorkshire). Lisle in 1835 had considerable distinction as a manufacturing town, at that time having in operation three gristmills, twenty sawmills, one oil cloth mill, three fulling mills, three carding mills, one trip hammer or forging mill, three tanneries and two places where potash was made.
46 years later (1876), Lisle's population had fallen dramatically to 400, likely because of a flood, but the exact reason for this decline is unknown.
In 1915 a home for children, "Happy Valley Homes", was established in the town.
The flood of 1935 destroyed a large part of the town, and often items from the 1935 flood are still being discovered, and displayed at the Maple Festival (Marathon) every year. Within and near the village of Lisle, this type of turmoil is unlikely to happen again because of dike-building and other flood control work along the Tioughnioga River and tributaries, which was accomplished in conjunction with construction of the Whitney Point dam on the separate Otselic River watershed (authorized under the Flood Control Act of June 22, 1936).
The history of Lisle is marked by population decreases: the abandonment of the Torry Lot, the fall of the Lisle mills, the flood of 1935.
Today however, with the rediscovery of gas, the population is slightly increasing again and the area tends to financially go in a different direction then the rest of the country.