The brothers came to the Genesee Valley from Connecticut as agents of their uncle, Colonel Jeremiah Wadsworth, to care for and sell the land he purchased.

The Wadsworths were participants in the negotiations of the Treaty of Big Tree between Robert Morris and the Senecas at the site of Geneseo in 1797.

A portion of the village was designated a National Historic Landmark by the United States Department of the Interior in 1991.

By 1835, the village consisted of 83 families, and the streets were Main, Second, North, South, Center and Temple Hill.

The advent of the State Normal School in 1871 brought a surge of development, and Oak Street opened in the late 1880s.

During World War II, a prisoner-of-war camp was built in Geneseo; it housed mostly Italian soldiers.

[4] In its addition of Geneseo to the National Register of Historic Places in 1991, the National Park Service said,[6] One of the most remarkably preserved villages in northwestern New York, Geneseo is one of the best examples of "picturesque" architecture and town planning as expounded by American landscape architect Andrew Jackson Downing (1815−1852) in his enormously popular and influential books.

The cohesive quality of the surviving town displays a textbook of styles and is almost unique in American architectural history.

The relatively sophisticated and imposing structures included in the district reflect the village's early-19th century prosperity as a market place for the valley's farming communities.The valley of the Genesee is wide and fertile, with some of the best agricultural land in New York, but it was prone to flooding, and Geneseo suffered several bad floods until the Army Corps of Engineers' construction of the Mount Morris Dam upstream of the community in the 1950s.

[9] One of the village's landmarks, a fountain in the middle of Main Street built in the 1880s, was damaged when a tractor trailer crashed into it on April 7, 2016.

According to the United States Census Bureau, the village has a total area of 2.9 square miles (7.4 km2), all land.

The Person of Interest TV series (2011–2016)[17] featured a three-second clip of Geneseo's Main Street.