The Mississippi River and Mark Twain are practically synonymous in American culture. Known as "America's river," the popularity of Twain's steamboat and steamboat pilots on the ever-changing Mississippi has endured prominently over the years.

Samuel Clemens became a licensed river pilot at the age of 24 under the apprenticeship of Horace Bixby, pilot of the Paul Jones. His name, Mark Twain, was derived from the river pilot term describing safe navigating conditions or "mark two fathoms". This term was shortened to "mark twain" by the leadsmen whose job it was to monitor the water's depth and report it to the pilot.

Although Mark Twain used his childhood experiences growing up along the Mississippi in numerous works, nowhere is the river and pilot's life more thoroughly described than in Life on the Mississippi.