Bednarik subsequently attended the University of Pennsylvania in Philadelphia, where he was a 60-minute man, excelling as both center and linebacker, as well as occasional punter. He was a three-time All-American, and was elected a member of the College Football Hall of Fame, as were two of his teammates on the 1947 squad—tackle George Savitsky and tailback Tony Minisi—and his coach, George Munger. At Penn, he also was third in Heisman Trophy voting in 1948 and won the Maxwell Award that year. In 1969, he was voted by a panel of sportswriters, coaches and hall of fame players as “The Greatest Center of All-Time.”

Bednarik was the first player drafted in the 1949 NFL Draft, by the Philadelphia Eagles, starring on both offense (as a center) and defense (as a linebacker). He was a member of the Eagles’ NFL Championship teams in 1949 and 1960. In the final play of the 1960 NFL Championship Game, Bednarik, the last Eagle between Green Bay’s Jim Taylor and the end zone, tackled Taylor at the Eagles’ eight-yard line, and remained atop Taylor as the final seconds ticked off the clock, ensuring the Packers could not run another play and preserving a 17–13 Eagles victory. The controversy surrounding this play led to the NFL putting in a rule penalizing defensive players for not allowing an offensive player from getting up off the field.

In 1960, Bednarik knocked Frank Gifford of the New York Giants out of football for over 18 months, with one of the most famous tackles in NFL history. Bednarik was criticized after the game by Giants players and fans for apparently celebrating Gifford’s injury and a picture from Sports Illustrated became iconic, showing Bednarik in mid-celebration, right above Gifford as he laid on the field, unconscious. Bednarik defended himself by saying that he was celebrating the fumble caused by the hit, which the Eagles recovered and was going to clinch the game for them, and the right to play for the NFL Championship. Years later, Gifford called the hit “a clean shot”, and said, “Chuck hit me exactly the way I would have hit him.”

When the Eagles established their Honor Roll in 1987, Bednarik was one of the first class of inductees. He attended reunions for the 25th anniversary of the 1960 NFL Championship team in 1985 and the 40th anniversary of the 1948–49 NFL Championship team in 1988 (though he had not played for the 1948 team), held in pregame ceremonies at Veterans Stadium.

Bednarik quarreled with current Eagles owner Jeffrey Lurie in 1996. Lurie refused to buy 100 copies of Bednarik’s new book for $15 each for the entire team, as that was against NFL rules, and that grudge carried over into the Eagles’ Super Bowl appearance in 2005, when he openly rooted against his former team. He was a consistent critic of several league issues, including his pension, today’s salaries, and one-way players.

In 1999, he was ranked number 54 on The Sporting News’ list of the 100 Greatest Football Players. This made him the highest-ranking player to have spent his entire career with the Eagles, the highest-ranking offensive center and the eighth-ranked linebacker in all of professional football.

In 2010, Bednarik was ranked number 35 on the NFL Network’s “The Top 100: NFL’s Greatest Players”. Ranked one spot ahead of Bednarik at #34 was Deion Sanders, a player for whom Bednarik has held open contempt in regards to being a two-way player. Bednarik was not the highest placed Eagle on the NFL Network’s list. That distinction was held by Reggie White at number 7.

On March 26, 2011, Bednarik was reportedly taken to St. Luke’s Hospital in Bethlehem. Hospital spokesmen stated that he was “in serious condition”, but did not give any further details. The next day, however, it was announced that he was doing fine and had no pre-existing medical conditions. His son-in-law stated that he had passed out from shortness of breath and low blood pressure, but did not suffer a heart attack or anything related and was expected to make a full recovery.

Bednarik died at 4:23 a.m. on March 21, 2015 after having fallen ill the previous day. He was 89. Although the Philadelphia Eagles released a statement saying he died after a “brief illness”, Bednarik’s eldest daughter, Charlene Thomas, disputed that claim. She said he had Alzheimer’s disease, had been suffering from dementia for years, and that football-related injuries played a role in his decline.