In 1980 the book was adapted as a TV movie for American public television, with David Knell performing as Sam Clemens (Mark Twain's real name), and Robert Lansing as Horace Bixby, the steamboat pilot who mentored him. The film used many tall tales from the book, woven into a fictional narrative.
In 2010, Life on the Mississippi was adapted as a stage musical, with book and lyrics by Douglas M. Parker and music by Denver Casado. It was produced that year in Kansas City, Missouri and Door County, Wisconsin.