The community's name means either "rattlesnake" or "Home of the Young Eagle" in Sioux. The first white settler in the area was George Wallace Jones, who purchased land for a leadsmelter in 1827. He soon sold the land to Samuel Mazzuchelli, who subsequently built a men's college in 1846. Mazzuchelli founded the Sinsinawa Dominican Sisters in 1847. This religious order founded a women's college and high school in Sinsinawa in 1865.