His coaching career began with the Bears in 1947, when he became an assistant coach to George Halas. After just two seasons with Chicago, Wilson left in 1949 for another assistant coaching position with the Detroit Lions, a division rival of the Bears. Prior to the 1957 season, he succeeded Buddy Parker as head coach. In his first year as head coach, Wilson guided Detroit to an 8–4 season and victory in the 1957 NFL Championship Game, the most recent league championship for the Lions. For his efforts, Wilson was awarded the first Associated Press NFL Coach of the Year Award. He remained with the Lions until 1964, though they were unable to replicate their success of 1957. Wilson then served for one year as an assistant coach to the Washington Redskins in 1965. Shortly after the season ended, Miami Dolphins owner Joe Robbie hired Wilson as the first head coach of the new AFL franchise in 1966. His son, George Wilson Jr., was a starting quarterback during the team's first season. Wilson, Sr. was unable to obtain a winning record in his four seasons with Miami. He was fired in February 1970 and replaced by Don Shula.