His older brothers, Lou (a future member of the Redskins) and Ted (who later played with the Bears and Lions), had played at Purdue but later Ted transferred to Indiana. Because of this, Alex said, "Indiana had the inside track" on recruiting him. Shortly after he graduated from high school, three coaches from the Iowa Hawkeyes met Karras at his brother Louie's house with an airplane and flew him to Spencer, Iowa, where he remained incommunicado through the summer. Writing in the Detroit Free Press in 1971 (as reprinted in the Iowa City Press-Citizen), Karras said that "nobody knew where I was, not even my mom, although Louie told her not to worry. Obviously, Iowa came up with something, I have no intention of stirring up any mess. I'll only say that, as Louie explained it, some accommodations were made by the people at Iowa that would make things easier for the family, and so away I went. It was the beginning of some awful years."
Following his release by the Lions in 1971, he made several more appearances on The Tonight Show Starring Johnny Carson and also played a bit part in The Mary Tyler Moore Show, appearing in the farewell party scene where Rhoda moves back to New York. Karras soon began acting on a full-time basis, playing a Tennessee boy turned Olympic weightlifter named Hugh Ray Feather in 1973's The 500 Pound Jerk. He played a hulking villain who menaced Clint Walker in the ABC TV film Hardcase. A minor but memorable role came one year later in the western parody Blazing Saddles (1974): the very strong and slow-witted thug Mongo, who rode into town on a huge brahman (marked with "yes" and "no" passing signals), knocked out a horse with one punch. (Mongo was also surprisingly philosophical, stating that he was "only pawn in game of life." This line was much-quoted upon Karras' death.) In 1974 he also played the part of Lyle, a Marine saved by Hawkeye Pierce in M*A*S*H. That same year, he was quickly brought in by ABC in September to replace Fred Williamson as a commentator for the network's Monday Night Football. He served three years in that role until leaving after the 1976 season, with his most memorable comment coming in his first game, when he joked that bald Oakland Raiders' lineman Otis Sistrunk, who never attended college, was from "the University of Mars", after seeing steam coming off his head.