During his freshman season, Peterson broke many NCAA freshman rushing records, rushing for 1925 yards and leading the nation in carries with 339. He was a finalist for the Heisman Trophy, finishing second to USC quarterback Matt Leinart, which was the highest finish ever for a freshman. He was also a finalist for the Doak Walker Award. Among other honors include being the first Oklahoma freshman recognized as a First-Team Associated Press All-American. Peterson contributed to an undefeated season for the Oklahoma Sooners and participated in the 2005 BCS National Championship Game with a berth to the FedEx Orange Bowl.
Peterson's playing time in 2005 was limited by a high ankle sprain. He injured his ankle in the first Big 12 Conference game of the season against Kansas State University. Despite missing time in four games, he rushed for 1,208 yards and fourteen touchdowns on 220 carries, finishing second in Big 12 rushing yardage. His 2005 season was also notable for a career-long eighty-four yard touchdown run against Oklahoma State University. Upon the conclusion of the season, he was named a member of the All-Big 12 Conference team.