Various sections of Roughing It were borrowed by television series such as Bonanza. In 1960, an hour-long adaptation was broadcast on NBC starring Andrew Prine and James Daly.
A four-hour 2002 mini-series adaptation was broadcast on Hallmark Channel. Directed by Charles Martin Smith; it starred James Garner as an elderly Samuel Clemens and Robin Dunne as a young Clemens.
A gold strike by Mark Twain and Calvin Higbie, which was seized by claim jumpers ten days after it was discovered, is recounted in Roughing It. In the dedication of the book, Twain refers to Higbie as an "Honest Man, a Genial Comrade, and a Steadfast Friend … dedicated in Memory of the Curious Time When We Two Were Millionaires for Ten Days". The prospecting story is also covered in a 1968 episode of the syndicated television anthology series, Death Valley Days, hosted by Robert Taylor. In the television dramitazation, Tom Skerritt played Twain, and Dabney Coleman was cast as Higbie.