His mother was Clora (née Casey) and his father was Ernest David Kelley, a Baptist minister of Irish ancestry.

[6] Before the end of his first year at Conyers, Kelley was regularly putting to use his musical talents, and often sang solo in morning church services.

As a result of Kelley's radio work, he won an engagement with Lou Forbes and his orchestra at the Paramount Theater.

[8] He made his film debut in the chorus of New Moon (1940), and nearly secured the lead role in This Gun for Hire (1942), but Alan Ladd was chosen instead.

While in California, Kelley was spotted by a Paramount Pictures scout while appearing in a United States Navy training film.

[12] The low-budget movie was a hit, bringing him to the attention of a national audience and giving Kelley reason to believe he would soon become a star.

[14] He played ranch owner Bob Kitteridge in the 1949 episode "Legion of Old Timers" of the television series The Lone Ranger.

In 1957, he had a small role as a Southern officer in Raintree County, a Civil War film directed by Edward Dmytryk, alongside Elizabeth Taylor, Montgomery Clift, and Lee Marvin.

[17][18] He also appeared in leading roles as a U.S. Navy submarine captain in the World War II-set television series, The Silent Service.

[9] His third appearance was in a third-season Star Trek episode (broadcast originally on October 25, 1968), titled "Spectre of the Gun", this time portraying Tom McLaury.

[20] Kelley, known to colleagues as "Dee",[21] also appeared in episodes of The Donna Reed Show, Perry Mason, Tales of Wells Fargo, Wanted: Dead or Alive, Boots and Saddles, Dick Powell's Zane Grey Theatre, Death Valley Days, Riverboat, The Fugitive, Lawman, Bat Masterson, Gunsmoke, Have Gun – Will Travel, The Millionaire, Rawhide, and Laredo.

[27] Kelley also appeared in at least one radio drama, the 1957 episode of Suspense entitled "Flesh Peddler", in which series producer William M. Robson introduced him as "a bright new luminary in the Hollywood firmament".

In 1963, he appeared in The Virginian episode "Man of Violence" as a "drinking" cavalry doctor with Leonard Nimoy as his patient.

In 1987, he also had a cameo in "Encounter at Farpoint", the first episode of Star Trek: The Next Generation, as Admiral Leonard McCoy, Starfleet Surgeon General Emeritus.

[40] Like other Star Trek actors, Kelley received little of the enormous profits that the franchise generated for Paramount, until Nimoy, as executive producer, helped arrange for Kelley to be paid $1 million for Star Trek VI: The Undiscovered Country (1991), which was his final live-action film appearance.

In a TLC interview done in the late 1990s, Kelley joked that one of his biggest fears was that the words etched on his gravestone would be "He's dead, Jim".

They met in 1942 when both were actors in a play and remained married for nearly 55 years until Kelley's death, living in a humble one-story ranch house in Sherman Oaks, California.

[47] Kelley was diagnosed with stomach cancer in 1997,[48] from which he died on June 11, 1999, aged 79, attended by his wife at the Motion Picture and Television Country House and Hospital in Woodland Hills, Los Angeles.