He played college football for the Alabama Crimson Tide, and was selected by the Carolina Panthers in the third round of the 2005 NFL draft.

[1] Mathis also played for the Miami Dolphins, Cincinnati Bengals, Philadelphia Eagles, Denver Broncos and Arizona Cardinals.

In April 2001, he was named the Paul Crane Most Improved Offensive Lineman for Alabama along with tight end Theo Sanders.

He helped anchor an offensive line that paved the way for the Crimson Tide to lead the Southeastern Conference in rushing yards per game in 2004.

Mathis was signed by the Miami Dolphins on September 9, 2008, after Donald Thomas, their rookie starting right guard spot was put on injured reserve.

[15] In 2013, Pro Football Focus chose Mathis for its inaugural Bruce Matthews Award recognizing the NFL's best offensive lineman.

[23] Mathis's uncle is Bob Baumhower, who played defensive tackle for Alabama and the Miami Dolphins.

On April 19, 2018, Mathis sold a 1952 Topps Mickey Mantle baseball card via Heritage Auctions for $2.88 million.