For the third straight season South Florida entered its bowl game with a 7–5 record. The 2010 Meineke Car Care Bowl marked the 6th straight season that the Bulls played in the postseason. After some struggles early on, the Bulls took off late. They won four of their final six, including an overtime victory at Miami, and nearly knocked off league champion Connecticut. This was South Florida's second appearance in the Meineke Car Care Bowl. They were a 14–0 loser to NC State in the 2005 game, the school's first ever bowl appearance.
The Tigers came into the game with a 6–6 record following a 2009 season in which they were the ACC Atlantic Division Champions. Clemson ranked No. 9 nationally in scoring defense, allowing just 17.75 points per game, but lost three of their final five, including the season finale to rival South Carolina. This was the Tigers first appearance in the Meineke Car Care Bowl.
The bowl game marked the first ever meeting between the two schools.