The history of Jefferson College includes the contributions of two of the area's most famous citizens, John Canon and Reverend John McMillan. McMillan had been giving instruction in his log cabin school on his property near Chartiers Hill Church and that school was the building block for higher education in the area. In 1791, John Canon offered a lot in his town and a building to be used for the construction of an academy. That became the Canonsburg Academy and Library Company in 1794. The academy grew quickly. Increases in the student body, the faculty and course offerings soon had this new venture offering college level education to those who enrolled.
On January 15, 1802 the former Canonsburg Academy became the Jefferson College when a charter was obtained from the Pennsylvania legislature.
Three fraternities were founded at Jefferson College. Two of those are still in existence locally.