Erwin began acting in college in the 1920s, having first appeared on stage. From there, he acted in stock theater in Los Angeles.
He broke into films in 1928 in Mother Knows Best. In 1934, he was cast as Joe Palooka in the film Palooka. In 1932, he co-starred with Bing Crosby in the comedy The Big Broadcast, where he played Texas oil tycoon Leslie McWhinney. In 1936, he was cast in Pigskin Parade, for which he was nominated for the Academy Award for Best Supporting Actor. In 1940, he played Howie Newsome, the dairy delivery vendor, in the film adaptation Our Town, based on the Thornton Wilder play.
In 1946, Erwin starred in Phone Again Finnegan on CBS. He played an apartment house manager in the comedy-drama.
In 1950, Erwin made the transition to television, in which he starred in Trouble with Father, which was retitled The Stu Erwin Show, with his co-star and real-life wife, Actress June Collyer. In 1963-1964, he played Otto King on The Greatest Show on Earth.
Erwin has a star at 6270 Hollywood Boulevard in the Television section of the Hollywood Walk of Fame. It was dedicated February 8, 1960.
Erwin made four guest appearances on CBS's Perry Mason, including the role of murderer Clem P. "Sandy" Sandover in the 1962 episode "The Case of the Double-Entry Mind", and murderer Everett Stanton in the 1964 episode, "The Case of the Scandalous Sculptor."
Erwin died of a heart attack on December 21, 1967, in Beverly Hills, Los Angeles, California, at age 64, and was interred at the Chapel of the Pines Crematory in Los Angeles.
