Prentice was redshirted his freshman year. The next year, Prentice had a very productive season even though he never broke into the starting line-up. In his first game, he ran for 102 yards and two touchdowns; for the season he ran for 601 yards on 123 carries and 12 touchdowns. In his sophomore year, Prentice earned a spot in Randy Walker's starting line-up and rushed for 1549 yards and 25 touchdowns. He was named first team All-Mid-American Conference and was one of eight semifinalists for the Doak Walker Award. In Prentice's junior year he ran for 1787 yards and 19 touchdowns while leading the RedHawks to a 10-1 season. Once again he was one of eight semifinalists for the Doak Walker Award. He was edged by Marshall's Chad Pennington in the MAC's Vern Smith Award for player of the year. His senior year was under a new head coach, Terry Hoeppner, who installed a more open passing attack rather than relying on the running game. Prentice ran for 1659 yards and 17 touchdowns. In the process he broke several Division I-A scoring records and was named third team All-American by the Associated Press. Prentice ended his career at Miami with 5,596 yards on 1,138 carries and numerous school, conference and NCAA records. At one point he recorded 862 consecutive touches without a fumble. Prentice will become the fourth Miami RedHawk to have his football jersey retired on September 6, 2014 at halftime of the Eastern Kentucky game. The previous three players were Ben Roethlisberger, Bob Hitchens, and John Pont.
Notable games
;vs. Akron Prentice exploded for 376 rushing yards in a 32-23 win against Akron. This set the Mid-American Conference record for most yards in a single game. At the time it was the 6th highest rushing total in Division I-A history. On his final carry of the game he broke Ricky Williams' career records both for points scored and total touchdowns with a 72-yard touchdown run. ;At North Carolina Prentice helped lead the RedHawks to a 13-10 upset of the #12 ranked North Carolina Tar Heels, rushing for 162 yards and a touchdown. Most of his yards came in the second half, including several carries on the last drive that led to a last-second game-winning field goal by John Scott. It was the first time in ten years that one player rushed for more than 150 yards on UNC. ;At Virginia Tech Prentice helped Miami to a 24-17 win over then-undefeated and twelfth-ranked Virginia Tech. His numbers were not great, but he ran for a touchdown on a game-changing fake field goal that was named CNN's "play of the day."