During spring training with the former Washington Senators, Dante took drama classes at the University of Miami in Coral Gables, Florida. Bandleader Tommy Dorsey arranged a screen test for him at Metro-Goldwyn-Mayer. His first film, Somebody Up There Likes Me, was released in 1956. He changed his name at the urging of studio boss Jack L. Warner, who thought "Vitti" would not fit well on theater marquees. Warner suggested some first names, from which the actor picked "Michael". He chose the last name "Dante" because it had been used by some relatives.

Dante was cast twice in on the ABC/Warner Brothers western series, Colt .45, starring Wayde Preston. Dante and Forrest Lewis portrayed Davey Lewis and Willy Ford, respectively, in the 1957 episode "The $3,000 Bullet". Dante then played the role of Ab Saunders in the 1958 episode "The Deserters", with Angie Dickinson as Laura Meadows and Myron Healey as an unnamed fur trader, and directed by Leslie H. Martinson. He also appeared on the ABC-WB crime drama, Bourbon Street Beat, with Andrew Duggan, on the syndicated adventure series, Rescue 8, starring Jim Davis and Lang Jeffries, and in three episodes of CBS's The Texan, starring Rory Calhoun.

Dante made two guest appearances on Perry Mason starring Raymond Burr. In 1959 he played Arthur Manning in "The Case of the Dangerous Dowager", and in 1965 he played murder victim Douglas Kelland in "The Case of the Feather Cloak."

A frequent extra on the original Star Trek television series, he was cast in the role of Maab" in the 1967 episode, "Friday's Child" alongside Julie Newmar. Dante has appeared at Star Trek conventions. He also had a recurring role as the Sioux Chief Crazy Horse in the short-lived ABC military western series, Custer starring Wayne Maunder in the title role of Lieutenant Colonel George Armstrong Custer.

In 1969, he played Clay Squires, a bitter young half-breed man, in the episode "Long Night at Fort Lonely" on the syndicated Death Valley Days, with Robert Taylor as Ben Cotterman and June Dayton as Cotterman's wife, Rachel.

In the 1970s, Dante met John Wayne, whom he watched on screen as a child. Wayne had seen Dante in Winterhawk and asked him to co-host a charity event in Newport Beach, California. That started a friendship between the two actors, and they co-hosted other events until Wayne's death in 1979.

Michael Dante is currently the host of a syndicated radio talk show, On Deck, previously known as the Michael Dante Celebrity Talk Show on which he interviews some of Hollywood's biggest stars. His program guests have included Milton Berle, Tony Curtis, and Bryant Gumbel. An avid Golfer, he once hosted the annual Michael Dante Celebrity Golf Tournament, a charitable fund-raiser held annually in Palm Springs, California, beginning in 1991.

In 2006, Dante told an interviewer that he had written a script for a sequel to Winterhawk and was trying to get funding for the projected movie.