Founded by the Society of Jesus in 1946, and named after the Jesuit missionary Simon Le Moyne, the college has graduated more than 35,000 students as of 2021.

[6] Walter A. Foery, the Roman Catholic Bishop of Syracuse, helped bring about the formation of Le Moyne College.

[8] Le Moyne College's 160-acre (0.65 km2)[9] campus is mostly located in the De Witt census-designated place,[10] in the suburban town of DeWitt, including all of the buildings used for academic purposes.

[5] Le Moyne College begins every academic year with two rituals: (1) 'Moving In Weekend,' when current students help to carry the boxes and suitcases of the new, first-year students into the dormitories; and (2) the Mass of the Holy Spirit, which continues a tradition dating back to the first Jesuit school, established in Messina, Sicily, in 1548 (probably preceding this date).

Its environmentally-sound design features include day lighting, solar preheating, and thermal storage, resulting in the award of LEED-Gold certification.

[15] Previously, Le Moyne competed in the NCAA at the Division II level through the 2022–23 school year with 21 varsity teams, offering participation opportunities for over 340 students.

[16] Previously, Le Moyne competed in the Northeast-10 Conference in all sports,[17] but started a transition to Division I on July 1, 2023, as a new member of the NEC.