[5] For a time, he lived in Birmingham, Alabama, writing advertising copy for a women's clothing store by day and acting in a stock theater company at night.

[8] His other Broadway shows include Yellow Jack (1934), The Cat and the Canary (1935), Whiteoaks (1938), with Ethel Barrymore, and Without Love (1942), with Katharine Hepburn.

In 1942, he became a contract actor with Warner Bros.[10] He played many character roles in movies and television, including a film series of Warner Bros. featurettes called the "Santa Fe Trail" series such as Wagon Wheels West,[11] and as a mad scientist in the 1953 horror film The Neanderthal Man.

[14] Shayne portrayed Police Inspector William "Bill" Henderson on the 1950s TV series Adventures of Superman.

He appeared sporadically in the early episodes of the series, in part because he was accused by his second wife Mary Sheffield,[15] and came under HUAC scrutiny and was briefly blacklisted on unproven and unspecific charges of association with Communism.

[citation needed] Shayne died in 1992 of lung cancer at the Motion Picture Hospital in Woodland Hills, California.