That same year, he played the historical figure Buffalo Bill Cody in the episode "The Grand Duke" of the syndicated anthology series, eath Valley Days.

In 1961, John Lupton was cast in another episode of Death Valley Days titled "South of Horror Flats," where he portrayed Pinkerton agent Allen Hodges, who is hired by a ghost-plagued woman to assist her and her gold fortune in traveling to San Francisco.

In this episode, series character Jess Harper, played by Robert Fuller, encounters Powers, a stranger with a bounty on his head due to a fraudulent charge, as he had killed in self-defense.

In 1961, Lupton also took on the role of Dr. John "Buzz" Neldrum in the episode "A Doctor Comes to Town" of the comedy-drama Window on Main Street, which starred Robert Young as an author returning to his hometown after the loss of his wife and child.

Other film appearances were in Disney's The World's Greatest Athlete (1973) as the race starter, The Whiz Kid and the Carnival Caper (1976), The Young Runaways (1978) and The Secret of Lost Valley (1980).

He was featured from 1967 to 1980 on the daytime soap opera Days of Our Lives in a central role Dr. Tom (Tommy) Horton Jr. John Lupton has a star on the Hollywood Walk of Fame located on the west side of the 1700 block of Vine Street.