LSU had no real trouble in winning its first 6 games in 1959, though its offense was not as potent as 1958's. Its defense made up for it by being even stingier, allowing only 6 points in 6 games. In the 7th game of the season LSU faced its sternest test—undefeated Ole Miss on Halloween in Tiger Stadium. That game between No. 1 LSU and No. 3 Ole Miss was touted as 1959's "Game of the Year." Ole Miss held a 3–0 lead until the 4th quarter, often punting on first down due to the very wet conditions on the field. With about 10 minutes left in the game, Ole Miss punted and Billy Cannon took the punt at the LSU 11. Cannon charted a course along the Ole Miss sidelines, weaving between Rebel defenders, eluding tacklers, and racing towards the goal line for an 89 yard punt return score. Ole Miss then started a determined drive and marched down to the two yard line where it was 4th and goal with 18 seconds left. Ole Miss quarterback Doug Elmore was stopped at the one by Cannon and his teammates to ensure the 7–3 victory. However the next week, LSU lost its next SEC game against Tennessee at Knoxville, 14–13, when Cannon's attempt at a 2 pt conversion failed. The loss not only cost LSU a shot as repeating as national champion, it also denied them the SEC championship, which went to the Georgia Bulldogs and their scrambling quarterback, Fran Tarkenton. The Tigers defeated Mississippi State and Tulane to finish the season 9-1, and they were ranked No. 3 in the nation behind No. 1 Syracuse and No. 2 Ole Miss.
In the meantime Billy Cannon won the Heisman Trophy by one of the widest margins in the history of the trophy balloting at the time. The Tigers were invited to play in the Sugar Bowl, and their opponent was to be none other than Ole Miss, in a rematch. At first Paul Dietzel, LSU's coach, was not anxious to replay the Rebels, but he was persuaded to do so by the athletic director, Jim Corbett. By the time January 1 came, three LSU star players were injured, including quarterback Warren Rabb, and halfbacks Wendell Harris and Johnny Robinson. The Tigers were soundly beaten by the Rebels, 21–0, and were outgained 373-74.