After high school, Cannon enrolled in Louisiana State University (LSU) where he began his great football career. Billy Cannon played three seasons for LSU and led the team to their first College Football National Championship in 1958. The Tigers captured the football title after defeating Clemson 7-0 in the Sugar Bowl.
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After the 1959 football season, Billy Cannon was awarded the Heisman Trophy, the most prestigious and coveted award in college football. To earn this honor, Cannon gained 598 yards rushing, returned eights kickoffs for 191 yards, and scored seven touchdowns.
For his accomplishments on the LSU football team, Cannon’s jersey number, "20", was retired after the 1959 season. LSU had never before, and has never since, retired a player’s number.
Soon after Cannon’s senior season ended, he secretly signed a $50,000 contract with the National Football League's Los Angeles Rams. A few weeks later, Cannon signed another contract with the Houston Oilers of the American Football League for $100,000 a year.