The series was created by co-stars Chester Lauck (who played Columbus "Lum" Edwards) and Norris Goff (Abner Peabody). Lum always pronounced his own name as Ed'erds and was very annoyed if Abner or anyone brought up his full first name. The two characters performed as a double act, with Lum generally playing the straight man to Abner's attempts to break free from Lum's influence. As co-owners of the Jot 'em Down Store in the fictional town of Pine Ridge, Arkansas, the pair are constantly stumbling upon moneymaking ideas only to find themselves fleeced by nemesis Squire Skimp, before finally finding a way to redeem themselves. Lum and Abner played the hillbilly theme with deceptive cleverness.

In addition to the title characters, Lauck also played Grandpappy Spears and Cedric Weehunt while Goff played Abner, Squire Skimp, Llewelyn "Mousey" Grey, Dick Huddleston, and most of the other characters.

Lum and Abner, like most sitcoms of the era, had a live house band, in this case a string band in keeping with the show's hillbilly humor. Marshall Jones, before his adoption of the "Grandpa" persona that made him famous years later, was among the band's first members.