He appeared in the films South Pacific (1958), Damn Yankees (1958), The Apartment (1960), Kiss Me, Stupid (1964), Paint Your Wagon (1969), The Sting (1973), Popeye (1980), Fast Times at Ridgemont High (1982), and Of Mice and Men (1992).

He mostly played small roles with stock companies, where he not only starred in traveling shows, but also worked at a movie theater, selling tickets and cleaning the stage floors.

[6] In 1949, he appeared in the short-lived play Mrs. Gibbons' Boys, directed by George Abbott, who later cast him as Satan (who bore the name "Mr. Applegate") in the 1955 musical Damn Yankees opposite Gwen Verdon as his sexy aide Lola.

In 1957, actress and producer Katharine Cornell placed him in a role on Broadway in Robert E. Sherwood's Pulitzer Prize winning play about the Hungarian Revolution of 1956, There Shall Be No Night.

[1] His other films included Kiss Them for Me; South Pacific; Say One for Me; Tall Story; Portrait in Black; The Apartment; Convicts 4; Wives and Lovers; Who's Minding the Store?

Walston achieved his greatest success as the title character (Uncle Martin) on My Favorite Martian from 1963 to 1966, alongside co-star Bill Bixby.

He returned to character actor status in the 1970s and 1980s, and guest starred in such series as Custer, The Wild Wild West, Love, American Style, The Rookies, Mission: Impossible, Ellery Queen, The Six Million Dollar Man, Little House on the Prairie, and The Incredible Hulk, again with Bixby, in which Walston played Jasper the Magician in an episode called "My Favorite Magician".

In a 1999 interview, Walston said that he was happy and relieved that when he walked down the street, young fans shouted at him "Mr. Hand" because he had finally torn away from his Martian role.

[12] In the first season episode, "Remembering Rosemary", Judge Bone wears a Martian costume with antennae to a Halloween party as a nod to Walston's infamous role as Uncle Martin.

In 1988, he guest starred in an episode of the popular horror-fantasy show Friday the 13th: The Series, as a bitter, elderly comic-book artist who uses a demonically cursed comic book to transform himself into a killer robot and murder his erstwhile enemies.

[13] He appeared in an AT&T long distance TV commercial in 1995, in which his dialogue implied he was Uncle Martin from Mars, looking for good rates to talk to fellow Martians living in the United States.

Walston made a guest appearance in an episode of Dr. Quinn, Medicine Woman entitled "Remember Me", in which he portrayed the father of Jake Slicker, who was stricken with Alzheimer's disease.