He played college football for the Ohio State Buckeyes and was selected by the Cardinals in the first round of the 2009 NFL draft with the 31st overall pick.

[14] He then followed that performance up with a 22 carry, 168 yard effort against Wisconsin, which included a 33-yard touchdown on the game's first possession and a 54-yard run to start the second half.

[27] In Week 1 of the 2009 season, Wells made his NFL debut with seven carries for 29 yards against the San Francisco 49ers in a 20–16 loss.

[30] In the Divisional Round of the playoffs, Wells scored his first postseason touchdown, a four-yard rush against the New Orleans Saints.

[33] For the 2011 NFL season, the Cardinals and coach Ken Whisenhunt placed a heavy emphasis on the ground-attack led by Wells.

The decision was mostly influenced by the departure of Tim Hightower to the Washington Redskins, in turn giving the starting back role to Wells.

[35] On November 27, 2011, in Week 12, Wells set a Cardinals single-game and personal record by rushing for 228 yards against the St. Louis Rams.

[36] Wells' performance eclipsed the team record previously held by LeShon Johnson, who rushed for 214 yards against the New Orleans Saints in 1996.

[39][40] On Sunday, November 25, 2012, Wells made his first appearance back from Injured Reserve for Arizona's game against the St. Louis Rams, scoring his first two touchdowns of the season.

After gaining three yards on four carries against the Chicago Bears in the penultimate game of the season,[42] Wells declared that he would be auditioning for the other 31 teams in his last appearance.