In 1964, George Lindsey got his big break as the slow-witted but kindly hick "Goober Beasley" on the now legendary The Andy Griffith Show. His character was renamed "Goober Pyle" to retain the same name as his cousin "Gomer Pyle", another slow-witted yokel played by Jim Nabors. Goober's antics frequently included his exaggerated "Goober Dance" and his comically bad Cary Grant impression ("Judy, Judy, Judy"). After Griffith left his television show, CBS retooled it as Mayberry R.F.D. and Lindsey played the same character until R.F.D. was cancelled in 1971. He guest starred on M*A*S*H as Roy Dupree, a Southern surgeon that worked the 8063rd that came to the 4077th when he had to switch places with Hawkeye Pierce.

Disney used his talents in a handful of projects, both as comedy support in features and giving vocal life to a few of their animated characters. Two Disney animated features that presented the voice of Lindsey were The Aristocats (1970) and Robin Hood (1973).

Lindsey became Goober for the third and last time in the long running country variety show "Hee Haw". He was with the series from 1972 to 1992.