In the 2003 season, Sproles continued to produce greatly for the Wildcats. In the season opener against California, he had 175 rushing yards and a rushing touchdown. On September 13, against Massachusetts, he had 152 rushing yards and three rushing touchdowns to help get the Wildcats to a 4–0 start. On November 8, in a game at Iowa State, he had 201 rushing yard and three rushing touchdowns. On November 22, against Missouri, he had 43 carries for 273 rushing yards and two rushing touchdowns. In the Big 12 Conference championship in 2003, a 35–7 win over #1 ranked Oklahoma, he had 235 rushing yards and 88 receiving yards and a receiving touchdown. Overall, he finished the 2003 season with 1,986 rushing yards and 16 rushing touchdowns. That same year, he finished fifth in the Heisman Trophy voting. He graduated with a degree in speech pathology. He led all FBS teams in rushing yards in 2003 with 1,986.