Most of Mahoney's films of the late 1940s and early 1950s were produced by Columbia Pictures. Like many a Columbia contract player, Mahoney worked in the studio's two-reel comedies. Beginning in 1947, writer-director Edward Bernds cast Mahoney in slapstick comedies starring The Three Stooges. Mahoney had large speaking roles in these films, and often played his scenes for laughs. In the Western satire Punchy Cowpunchers (1950), Mahoney, striking a heroic pose, would suddenly get clumsy, tripping over something or taking sprawling pratfalls. Beginning in 1950, Columbia management noticed Mahoney's acting skills and gave him starring roles in adventure serials. He was originally billed as Jacques O'Mahoney, then Jock O'Mahoney.
In 1948, Mahoney auditioned to play Tarzan after the departure of Johnny Weissmuller, but the role went to Lex Barker.
Cowboy star Gene Autry, then working at Columbia, hired Mahoney to star in a television series. Autry's Flying A Productions filmed 79 half-hour episodes of the syndicated The Range Rider from 1951 to 1953. In 1959 there was a lost episode shown six years after the series ended. He was billed as Jack Mahoney. The character had no name other than Range Rider. His series co-star was Dick Jones, playing the role of Dick West.
When Charles Starrett's contract ran out in the spring of 1952, Columbia decided to replace him with Mahoney, opposite Starrett's sidekick Smiley Burnette. The first film was completed but never released; Columbia abandoned the series in June 1952, bringing an end to its long history of B-Western production.
For the 1958 television season, he starred in the semi-western Yancy Derringer series for 34 episodes, which aired on CBS. Yancy Derringer was a gentleman adventurer living in New Orleans, Louisiana, after the American Civil War. He had a Pawnee Indian companion named Pahoo Katchewa ('pa-who-kaht'-chee-wah') ("Wolf Who Stands in Water") who did not speak, played by X Brands. Pahoo had saved the life of Derringer, and thereafter was responsible for Derringer's life.
Mahoney was married three times, first to Lorraine O'Donnell, with whom he had two children, Kathleen O'Mahoney and Jim O'Mahoney. He next married Actress Margaret Field on December 11, 1959, in Las Vegas. They had one child, Princess O'Mahoney, born in 1962. Margaret Field already had two children, Richard Field and Sally Field. Mahoney and Field divorced in June 1968. The following year, he married Actress Autumn Russell, who had three children, Carl Botefuhr, Angela Russell and Andrea von Botefuhr. They remained together until his death.
In 1960, Mahoney guest-starred in the Rawhide episode "Incident of the Sharpshooter." He also appeared in television guest-starring roles on such series as Batman, the Ron Ely Tarzan series, Hawaii Five-O, Laramie, and The Streets of San Francisco.
In 1962, Mahoney became the thirteenth actor to portray Tarzan when he appeared in Tarzan Goes to India, shot on location in India. A year later, he again played the role in Tarzan's Three Challenges, shot in Thailand. When this film was released, Mahoney, at 44, became the oldest actor to play the jungle king, a record that still stands. Dysentery and dengue fever plagued Mahoney during the shoot in the Thai jungles, and he plummeted to 175 pounds. It took him a year and a half to regain his health. Owing to his health problems and the fact that Producer Weintraub had decided to go for a "younger look" for the apeman, his contract was mutually dissolved.
Mahoney made three appearances on the Ron Ely Tarzan series--The Ultimate Weapon (1966), The Deadly Silence (1966) (a two-part episode, later edited into a feature film) and Mask of Rona (1967).
In 1973, he suffered a stroke at age 54 while filming an episode of Kung Fu, but recovered.
In the 1980s, Mahoney made guest appearances on the television series B. J. and the Bear and The Fall Guy. During the final years of his life he was a popular guest at film conventions and autograph shows. He died of another stroke two days after being involved in an automobile accident in Bremerton, Washington at the age of 70. His ashes were scattered into the Pacific Ocean.
In 1981, Mahoney returned to the Tarzan film series as the stunt coordinator on the John Derek-directed remake of Tarzan, the Ape Man. He was billed as "Jack O'Mahoney".
A tribute to Mahoney entitled "Coming Home" is found on the Internet site of the late marksman Joe Bowman of Houston, a close Mahoney friend. On February 6, 1990, the poem was read at a memorial tribute to Mahoney held at the Sportsmen's Lodge in Studio City, California. More than 350 attended, included Bowman. The reading was conducted by Mahoney's widow, Autumn O'Mahoney.