Lilly played college football at Texas Christian University (TCU), where he was a two-time All-Southwest Conference pick and a consensus All-American. He was a 1961 member of the College Football All-America Team and was a 2006 inductee to the East-West Shrine Game Hall of Fame. Lilly was inducted into the College Football Hall of Fame in 1981. As a first-round draft pick in the 1961 NFL Draft, and the first draft pick in Dallas Cowboys franchise history, Lilly went on to be All-Pro seven times, and was selected to play in 11 Pro Bowl games.
Lilly made the adjustment in the pros becoming the main man in Dallas's vaunted "Doomsday Defense". As a tackle, Lilly was a first-team All-NFL choice every year from 1964 through 1969, then again in 1971. In 1972 he and the rest of the Cowboys won the Super Bowl against the Miami Dolphins, 24-3. His 29-yard sack of Dolphin quarterback Bob Griese is one of the most memorable plays in Super Bowl defensive history. This was the signature play of his 14-year hall-of-fame career.
Affectionately known as "Mr. Cowboy," his name was the first inscribed in the "Dallas Cowboys Ring of Honor", above Texas Stadium and the current Cowboys Stadium. Emmitt Smith, Mel Renfro, Tony Dorsett, Randy White, Roger Staubach, Michael Irvin, Troy Aikman, Drew Pearson and Charles Haley are also members of the Cowboys Ring of Honor. The Cowboys had a Bob Lilly Day on November 23, 1975, to honor him and make Lilly the first inductee into The Ring of Honor.
Lilly was inducted into the Pro Football Hall of Fame in 1980, his first year of eligibility, and was the first player who spent his entire career with the Cowboys to be elected to the Pro Football Hall of Fame. He is a member of the National Football League 1960s All-Decade Team and National Football League 1970s All-Decade Team.
In 1999, he was ranked number 10 on The Sporting News' list of the 100 Greatest Football Players, the highest-ranking defensive lineman and the highest-ranking Cowboy. Sports Illustrated named him one of the ten most revolutionary defensive players.