Portage Des Sioux is a city in St. Charles County, Missouri, United States. The town sits on the Mississippi River roughly opposite Elsah, Illinois, and is the home of the riverside shrine of Our Lady of the Rivers. The population was 328 at the 2010 census. The city was founded in 1799 by Spanish Lt. Gov. Zenon Trudeau and François Saucier in reaction to American plans to build a military post about twelve miles (19 km) downstream. The French name derives from the overland escape route between the Missouri River and Mississippi River used by a band of Sioux, fleeing enemies; they used this area as a portage for their canoes, outdistancing their rivals who instead paddled all of the way to the confluence of the rivers.

St. Charles County is in the central eastern part of the U.S. state of Missouri. As of the 2020 census, the population was 405,262, making it Missouri's third-most populous county. Its county seat is St. Charles. The county was organized October 1, 1812, and named for Saint Charles Borromeo, an Italian cardinal.