In 1939, Tobias signed with Warner Brothers and was cast in supporting roles, many times along with James Cagney, in such movies as Cagney's Yankee Doodle Dandy (1942) as well as with Gary Cooper in Sergeant York (1941) and Irving Berlin, Ronald Reagan, and George Murphy in This Is The Army (1943).
From 1959 to 1961, Tobias played Penrose in eight episodes of the ABC television series, Adventures in Paradise, starring Gardner McKay. Later in the 1960s, he played the long-suffering neighbor, Abner Kravitz, on the ABC sitcom, Bewitched.
Tobias often appeared in a uncredited role as a courtroom spectator on CBS's Perry Mason. He played Sidney Falconer in the 1964 Perry Mason episode, "The Case of the Antic Angel."
George Tobias never married and retired from acting in 1977 after a guest role in the Bewitched sequel Tabitha.
On February 27, 1980, Tobias died of bladder cancer at the age of 78 at Cedars Sinai Medical Center in Los Angeles, California. He is buried in Mount Carmel Cemetery, Glendale, Queens, New York City.