People have lived on the terrace between Moccasin Bluff and the St. Joseph River for eight thousand years. The first inhabitants stayed in small temporary camps as early as 6300 B.C. The residents of A.D. 500 traded with groups in Indiana and Illinois. Those living here 600 to 900 years ago farmed and had more permanent villages. In 1977 Moccasin Bluff was listed on the National Register of Historic Places because of its archeological importance.
As white settlers began to farm and log the St. Joseph River Valley in the late 1820s, the federal government adopted a policy of moving local Potawatomi Indians west. The bluff is said to be named for Cogomoccasin, leader of one of the permanent Potawatomi villages. River-boats were the valley's main source of transportation until, in 1881, the St. Joseph Valley Railroad was constructed along the route that became the Red Bud Trail.