The Mississippi River played an important role in the life of Samuel Clemens, who even adopted the steamboat captain's call to "Mark the twain!" as his pen name. As a child, the river gave Twain access to the outside world and influences beyond his immediate realm, and provided employment and adventure as Twain grew older. Given its importance, it is no surprise that the Mississippi River is a featured component of several of Twain's works, including Tom Sawyer and The Adventures of Huckleberry Finn.

The influence of the river is the same for the characters of Pudd'nhead Wilson, bringing the exotically foreign twins to town and allowing the people of Dawson's Landing to come and go. Yet the river is also the conduit to the slave trade, to gambling, and to other vices, and as such, it is a curse as well as a blessing. Being sold "down the river" to the cruel masters of the South is a constant fear for Missouri slaves, and because of this, the river plays the role of both enticing escape route and road to suffering.