Buttram went to Hollywood in the 1940s and became a sidekick to Roy Rogers. However, because Rogers already had two regulars, Buttram was dropped.
He was then picked by Gene Autry, recently returned from his World War II service in the U.S. Army Air Force, to work with him. Buttram co-starred with Autry in more than 40 films and in over 100 episodes of Autry's television show. Buttram's first Autry film was The Strawberry Roan in 1948. In the late 1940s, Buttram joined Autry on his radio show Melody Ranch and then on television with The Gene Autry Show. During the first television season, Buttram went by Pat or Patrick, with a variety of last names. From the second season forward, he used his own name.
Buttram also played Mr. Eustace Haney in the 1965–1971 television comedy Green Acres. He did voice work for several Disney animated features, playing Napoleon (hound dog) in The Aristocats, the Sheriff of Nottingham (a wolf) in Robin Hood, Luke (muskrat) in The Rescuers, Chief (hunting dog) in The Fox and the Hound, and one of the Toon bullets in Who Framed Roger Rabbit. He had a recurring role as the voice of Cactus Jake on Garfield and Friends. One of his later roles was a cameo in Back to the Future Part III. His final voice-over was A Goofy Movie, released a year after his death. Buttram is credited as one of the writers on the Hee Haw television show for two episodes in 1969 and 1970.
Buttram made the oft-quoted observation about the 1971 "rural purge", in which CBS canceled many programs with a rural-related theme or setting: "CBS canceled everything with a tree in it – including Lassie", referring to the cancellations of Green Acres, The Beverly Hillbillies and Petticoat Junction.