Stone began his career on Broadway in 1939 and appeared in five plays in the next six years, including One Touch of Venus and Stalag 17. His other Broadway credits include Morning Star (1939), A Bell for Adano (1944), S.S. Glencairn (1947), Abraham Cochrane (1963), Charley's Aunt (1970), and Ring Around the Bathtub (1971).

Stone made his motion picture debut in the Alan Ladd film noir classic The Blue Dahlia (1946). In 1949, he co-starred on the short-lived live television sitcom The Hartmans. He then went on to work in small but memorable roles in such films as The Harder They Fall (1956) with Humphrey Bogart, Alfred Hitchcock's The Wrong Man (1956), Somebody Up There Likes Me (1956), The Garment Jungle (1957), The Invisible Boy (1957), Spartacus (1960), The Chapman Report (1962), X: The Man with the X-ray Eyes (1963), The Greatest Story Ever Told (1965), Girl Happy (1965), The St. Valentine's Day Massacre (1967, as Frank Nitti), The Big Mouth (1967), The Seven Minutes (1971), Mitchell (1975), and Hardly Working (1980).

Stone made more than 150 guest appearances on numerous shows dating from the 1950s to the early 1980s, including but not limited to the following: U.S. Marshal, Stagecoach West (the 1960 episode "Red Sand" with Dean Jones), The Rifleman, Gunsmoke, Cimarron City, The Restless Gun, The Alaskans, The Barbara Stanwyck Show, Sugarfoot, The Islanders, The Tall Man, The Roaring 20's, Empire, I Spy, The Virginian, The Untouchables, Wanted: Dead or Alive, Mr. Novak, The Twilight Zone, Route 66, Have Gun – Will Travel, The Big Valley, Trackdown (3 episodes), Going My Way, Gilligan's Island, Hogan's Heroes, Hawaii Five-O, Mannix, Get Smart, Griff, Alfred Hitchcock Presents and Charlie's Angels.

On January 14, 1958, he played the brutal Rafe Larkin, "The Last Comanchero," in the ABC/Warner Brothers western television series, Cheyenne, with Clint Walker in the title role. In the storyline, Larkin is captured in the New Mexico Territory and has been jailed by Cheyenne Bodie, acting as a marshal, to await trial for the murder of a couple and the burning of their ranch house. Edd Byrnes plays Benji Danton, the son of the slain couple whose girlfriend is being held hostage by Larkin's only surviving son. The key to resolution of the story is illuminating material left by an itinerant Photographer seeking to capture the spirit of the Old West.

Although Stone went on to perform secondary roles in a number of films, he became a recognizable face to television viewers. He played Handyman in the comedy The Hartmans, Jake Goldberg in the drama The Goldbergs, and Lieutenant Hauser in the drama The Walter Winchell File. In 1959, he co-starred as a principal investigator in the syndicated series Grand Jury.x

Stone was married twice. His first wife, Jean, died in 1960. He and his second wife separated in 1964. He had two sons and one daughter.

In the 1961–1962 season, Stone appeared three times in Stephen McNally's ABC crime drama Target: The Corruptors!. In 1963, he appeared with Marsha Hunt in the ABC medical drama Breaking Point in an episode which was nominated for an Emmy Award for writing. In September 1964, he appeared in the Western series, Bonanza ("The Hostage"). Also in 1964, Stone appeared in Daniel Boone starring Fess Parker (in the episode entitled "The Fluellen Family" as Greenbriar).

In 1964, Stone was nominated for an Emmy Award for Outstanding Single Performance by an Actor in a Leading Role for his role in CBS's The Nurses.

In 1969-1970, Stone portrayed Hamilton Greeley in the NBC comedy series My World and Welcome to It. He played Sam Steinberg on the 1972-1973 CBS comedy Bridget Loves Bernie, and had the role of Charlie on the CBS comedy Joe and Sons (1975-1976).