St Charles was the location of the Indian community for the chief of the Pottawatomie that inhabited the area. A city park overlooking the river was dedicated to this Indian past. After the Black Hawk War in 1832, the entire area of the Fox Valley was opened to American settlement. Evan Shelby and William Franklin staked the first claim in what is now St. Charles in 1833. They came back in 1834 with their families from Indiana, and were joined by over a dozen other families later that year. The township was initially known as Charleston, but this name was already taken by the downstate city of Charleston, Illinois so the name of Saint Charles (suggested by S. S. Jones, a lawyer) was adopted in 1839. St. Charles became incorporated as a city in 1874

According to the United States Census Bureau, the city has a total area of 14.1 square miles (36.5 km2) of which, 14 square miles (36.3 km2) is land and 0.2 square miles (0.52 km2) is water. The total area is 1.13% water.