McCormack was drafted by the New York Yanks in the 1951 NFL Draft. After one year of play, he then served two years of military service in the United States Army before being traded to the Browns. In his first season with the team, he played on the defensive line, with his fumble recovery in the 1954 NFL Championship game against the Detroit Lions helping set up an important early touchdown.  The following season, he was shifted to offensive tackle and helped the Browns once again capture the NFL title. He would play a key role in helping legendary running back Jim Brown become one of the dominant players in the game, ending his career with four selections to the Pro Bowl.  Paul Brown. legendary Cleveland Browns founder, owner, and coach, stated in his 1979 memoir, PB: The Paul Brown Story, “I consider (Mike) McCormack the finest offensive tackle who ever played pro football.” Also, according to Paul Zimmerman’s 1984 book, The New Thinking Man’s Guide to Pro Football, Brown also stated that McCormack was the best offensive lineman he ever coached. The book states that McCormack “[c]ould handle the Colts’ Gino Marchetti better than any tackle in the game. Power combined with great intelligence and 4.8 speed. ‘I’ve seen him have games,’ former player and NFL executive Bucko Kilroy says, ‘where if you were grading him, he’d score 100. Not one mistake, and his guy would never make a tackle.'”

His coaching career began in 1962 with the first of four consecutive stints as an assistant in the annual College All-Star Game. In 1965, he was hired as an assistant coach with the Washington Redskins, spending the next eight seasons working under four different head coaches, including former teammate Otto Graham from 1966-1968.  In 1973, he was hired as head coach of the Philadelphia Eagles, but a 16-25-1 record over three seasons resulted in his dismissal following the conclusion of the 1975 season. He moved on to serve as an assistant with the Cincinnati Bengals from 1976-1979, then was hired as head coach of the Baltimore Colts in 1980. However, two frustrating seasons ended in his dismissal from the Colts.  In 1982, McCormack joined the Seattle Seahawks, eventually becoming president and general manager. He also served as the Seahawks interim head coach for the remainder of the 1982 season when Jack Patera was fired after the first two games. McCormack took over during the 57-day players strike and led the team to a 4-3 record, the only time he compiled a winning record as an NFL head coach. He then returned to his management position when the Seahawks hired Chuck Knox as their new head coach in 1983.

In January 1989, he was abruptly fired by the new Seahawks owner, Ken Behring, who explained the decision was necessary in order to make changes in the financial operations of the team. Later that year, McCormack became a consultant for Jerry Richardson and his ownership group that were seeking to land an NFL expansion team in Charlotte, North Carolina. In 1993, he was hired by the newly formed Carolina Panthers as their team president and general manager. He retired from the Panthers organization in 1997.  McCormack died of natural causes on November 15, 2013 in Palm Desert, California.