It opened on October 11, 1976[2] and was located at 914 N 1st Street, on the western bank of the Mississippi River, four blocks north of the Gateway Arch in Laclede's Landing.

Concerts at the venue, which held up to 1,000 people, were often "all ages" events,[1] with just over one percent restricted to patrons 21 and over.

George Thorogood & the Destroyers' album Live: Let's Work Together features tracks recorded at Mississippi Nights.

In early 2003, rumors began circulating that the club would close to make way for Horseshoe St. Louis (at the time known as Lumière Place), a new casino development.

The rumors were confirmed in early 2007, and the last show was held on January 19, 2007.