Sproles started the 2004 season off strong with 42 carries for 221 yards and a touchdown in a victory over Western Kentucky. On September 18, against Louisiana–Lafayette, he had 292 rushing yards and a touchdown. On October 23, against Nebraska, he had 135 rushing yards and two rushing touchdowns. On November 6, against Missouri, he had 160 rushing yards and two rushing touchdowns. In the final game of his collegiate career, against Iowa State, he had 167 rushing yards and a rushing touchdown. Overall, he finished the 2004 season with 1,318 rushing yards and 11 touchdowns.