He progressed from small Broadway parts to larger ones, eventually taking over the role of George from Wallace Ford in the 1937 production of Of Mice and Men.

Clark first appeared on television in the late 1940s, and after the mid-1950s worked much more in that medium than in feature films. In the 1954-1955 season, he co-starred as the character Richard Adams, with Gary Merrill in the role of Jason Tyler, in the NBC crime drama Justice, about attorneys of the Legal Aid Society of New York.

Clark was married twice: first, to Margot Yoder, Painter, from 1941 until her death in 1970; and second, to Geraldine Frank, former model, stockbroker, and real estate associate broker, from 1971 until his death in 1998.

Clark's first film was The Pride of the Yankees (1942). He had an uncredited bit in The Glass Key (1942) at Paramount.

He was third billed in Destination Tokyo (1943) beneath Cary Grant and John Garfield, and in The Very Thought of You (1944) with Dennis Morgan and Eleanor Parker. He had one of the leads in Hollywood Canteen (1944), playing an actual role while most Warners stars made cameo appearances as themselves. Clark had the lead in the 1944 short film I Won't Play with Janis Paige; it received the 1945 Academy Award for Best Short Subject (Two-Reel). Clark supported Morgan in God Is My Co-Pilot (1945) and Garfield in Pride of the Marines (1945).

Exhibitors voted Clark the 16th most popular star at the US box office in 1945.

Clark supported Bette Davis and Glenn Ford in A Stolen Life (1946) and was promoted to top billing for Her Kind of Man (1946), a crime film. He followed it with That Way with Women (1947), Deep Valley (1947), and Embraceable You (1948). Republic Pictures borrowed him to play the lead for Frank Borzage in Moonrise (1948). At Warner Bros., he was in Whiplash (1948). Clark went to United Artists for Without Honor (1948), then back to Warner Bros. for Backfire (1950) and Barricade (1950). He travelled to England to make Highly Dangerous (1950) and France for Gunman in the Streets (1951). Back at Columbia he was in Never Trust a Gambler (1951). He acted in the United Artists Western Fort Defiance (1951). He went back to Britain for The Gambler and the Lady (1953), Murder by Proxy (1954) and Five Days (1955), all for Hammer Films. In the US, he was in Go Man Go (1954) with the Harlem Globetrotters and Toughest Man Alive (1955).

During the 1950s, he became one of a small group of actors (excluding the original 'founding' members brought in at the Studio's inception) awarded life membership in The Actors Studio.

Clark played Peter Chambers in the short-lived radio show Crime and Peter Chambers, a half-hour show that aired from April 6 to September 7, 1954.

In 1955 he was acting on stage when the female he was acting against died in his arms.

He went back to films for The Man Is Armed (1956) and Outlaw's Son (1957).

In 1959, he reprised Humphrey Bogart's role as Slate in Bold Venture, a short-lived television series. He also guest starred on a number of television shows, including Faye Emerson's Wonderful Town, Appointment with Adventure, CBS's Rawhide in the episode "Incident of the Night Visitor", and The Twilight Zone, in the episode "The Prime Mover". In 1970, he guest-starred in an episode of The Silent Force and had a role in The McMasters (1970). He also played Lieutenant Tragg in the short-lived revival of the Perry Mason television series in 1973, and appeared in the 1976 miniseries Once an Eagle.

Clark died on September 11, 1998, of lung cancer at St. John's Hospital in Santa Monica, California. His remains were cremated and his ashes given to his widow.