His film career started in the early 1950s. Mike Connors was cast in the critically acclaimed John Wayne film, Island in the Sky in which he was a crewman on one of the search-and-rescue planes. In 1956, still billed as Touch Connors, he played an Amalekite herder in Cecil B. DeMille’s The Ten Commandments starring Charlton Heston. He appeared in numerous television series, including the co-starring role in the 1955 episode “Tomas and the Widow” of the NBC Western anthology series Frontier. He guest-starred on the early sitcoms, Hey, Jeannie! and The People’s Choice. He guest-starred in two Rod Cameron syndicated crime dramas, City Detective and the Western-themed State Trooper, and played the villain in the first episode filmed (but second one aired) of ABC’s smash hit Maverick opposite James Garner in 1957. In 1958, Connors appeared in the title role of the episode “Simon Pitt”, the series finale of the NBC Western Jefferson Drum, starring Jeff Richards as a frontier newspaper editor. He also appeared in another NBC Western series, The Californians. That same year, Mike Connors was cast as Miles Borden, a corrupt US Army lieutenant bitter over his $54 monthly pay, on NBC’s Wagon Train in the episode “The Dora Gray Story”, with Linda Darnell in the title role. About this time, he also appeared on an episode of NBC’s Western series Cimarron City.

Mike Connors appeared in other syndicated series: The Silent Service, based on true stories of the submarine section of the United States Navy; Sheriff of Cochise, set in and about Bisbee, Arizona; Whirlybirds, an aviation adventure series; and Rescue 8, based on stories of the Los Angeles County Fire Department. An episode of Studio 57 starring Connors and titled “Getaway Car” was proposed as a pilot for a series about the CHP to be called Motorcycle Cop. Connors also co-starred (as the villain) in the classic 1956 Roger Corman sci-fi film, The Day The World Ended, and also co-starred in Roger Corman’s Swamp Women that same year. Later, he was cast in the episode “The Aerialist” of the anthology series, Alcoa Presents: One Step Beyond. In 1963, he guest-starred as Jack Marson in the episode “Shadow of the Cougar” on the NBC modern Western series, Redigo, starring Richard Egan. In 1964, Connors appeared in a pinch-hit role for Raymond Burr as attorney Joe Kelly in the Perry Mason episode, “The Case of the Bullied Bowler”. In 1965, he co-starred in one of Robert Redford’s earliest film roles, a World War II black comedy, Situation Hopeless… But Not Serious alongside Sir Alec Guinness.

Mike Connors later took the starring roles in Tightrope! (1959–1960), Mannix (1967–1975), and Today’s F.B.I. (1981–1982). Mannix was originally produced by Desilu Productions (later absorbed by Paramount Television). Then-president Lucille Ball pushed for CBS to keep the show on air after a lackluster first season in the ratings. This move enabled the show to become a long-running hit for the network. Connors was able to work with his boss on-screen during a cross-promotion episode of Ball’s Here’s Lucy series in 1971, showing his skill at comedy. The episode, which opened Lucy’s fourth season, is entitled “Lucy and Mannix are Held Hostage”. This was notable as the first episode shot at Universal Studios, after Ball ceased producing her program at Paramount Studios. Mike Connors played Air Force Colonel Harrison “Hack” Peters in Herman Wouk’s 1988 World War II-based miniseries War and Remembrance. Connors’ final appearance was in a Two and a Half Men episode, where he played a love interest of Evelyn. Mike Connors died in Tarzana, California, a week after being diagnosed with leukemia, at the age of 91.