Willis was drafted by the Bills with the 21st pick in the 2003 NFL Draft, while still recuperating from a devastating knee injury he incurred in the 2003 Fiesta Bowl, while playing for the University of Miami. By week six of the 2004 NFL season, however, McGahee had fully recovered and supplanted Travis Henry as the Bills' starting running back.

At the University of Miami, he shattered several records in the 2002 season. He broke, substantially, school season records, carrying the ball 282 times for 1,753 yards (6.2 avg.) and 28 touchdowns, breaking the previous marks of 1,416 yards and 17 scores by Edgerrin James in 1998; only Nebraska's Mike Rozier (29 in 1983) and Oklahoma State's Barry Sanders (37 in 1988) ran for more touchdowns in a season in NCAA Division I-A annals. His 10 100-yard performances broke the Hurricanes' season record of eight, set by Ottis Anderson in 1978; he added 350 yards on 24 receptions (14.6 avg.) that season. He gained 2,108 all-purpose yards, breaking the old Miami season record of 1,708 by Anderson in 1978. McGahee was also a 2002 consensus All-American and All-Big East Conference first-team selection. He was a finalist for the Heisman Trophy, given to the nation's top player, finishing fourth in the voting (660 points).

McGahee is considered one of the NFL's most promising young running backs, and some believe he may be a candidate to break some of the most significant NFL rushing records. Some, however, still doubt that he has or ever will return to the form he showed prior to his leg injury. McGahee initally took the number 42, but then switched to number 21 to signify his draft selection.

McGahee's agent is fellow University of Miami alumnus Drew Rosenhaus, considered one of the most aggressive agents currently representing NFL players. Rosenhaus also represents former University of Miami stars such as Edgerrin James, Clinton Portis and Jeremy Shockey.