George was born in Waynesburg, Pennsylvania, about 50 miles south of Pittsburgh. He is among numerous legendary football players born in football-rich Western Pennsylvania. He attended college at Wake Forest University, and was the Bears' second-round draft pick in 1951. He began his pro football career the following year as a middle guard in the then-standard five-man defensive front. He was selected to play in eight consecutive Pro Bowls, from 1954 to 1961.
George is credited as the first true middle linebacker in football history and, inadvertently, the creator of the 4–3 defense. Noting during a 1954 game with the Philadelphia Eagles that his tendency to hit the center right after the snap led to the quarterback passing right over his head, he began to drop back from the line, not only enabling him to intercept and otherwise disrupt several passes from that game forward but also creating the familiar 4–3 setup (four linemen and three linebackers).
In addition to his 18 career interceptions, George also recovered 19 fumbles, and in 1954 scored 25 points on 13 PATs and four field goals. In 1963, he led the Bears defense when they won the NFL Championship.
George was elected to the Pro Football Hall of Fame in 1974. The Bears retired his uniform number 61. In a 1989 article, in which he named his choices for the best athletes ever to wear each uniform number from 0 to 99, Sports Illustrated columnist Rick Reilly not only chose George for number 61, but called him "the meanest Bear ever," no small thing considering the franchise's long history and reputation for toughness. In 1999, he was ranked number 49 on The Sporting News' list of the 100 Greatest Football Players. George was killed in an automobile accident in Rockford, Illinois on September 30, 1982.