Kimmswick was founded in 1859 by dry goods merchant Theodore Kimms, who named the town after himself. He laid the town out on on land purchased from the widow of Captain George Waters. The area was settled by German immigrant stonecutters and wealthy St. Louisans.
There are numerous salt springs in the area, which were used by Native Americans as a source of salt. These salt springs also attracted prehistoric animals; nearby is the Mastodon State Historic Site, where bones of this extinct elephant were discovered. A spa and resort area in Kimmswick was a popular steamboat daytrip destination for Saint Louisians in the late 19th century.
By the early 1970s, the town's existence was threatened by construction of Interstate 55 and flooding of the Mississippi River. The Kimmswick Historical Society, founded in 1969, was instrumental in saving the town and preserving its historic architecture. The town is now a popular tourist destination, and features numerous antique and craft stores and country-style restaurants. The Blue Owl is the most well known restaurant as it was once mentioned by Oprah in her O magazine. The town survived the Flood of 1993 by the efforts of many volunteers and government agencies. Kimmswick defeated a proposed casino to be built on the site, fearing that gambling would damage the town's character.
Kimmswick's Applebutter Festival is famous throughout the Midwest. It typically takes place in late October.