Although he bulked up from to after signing with Alabama in February 2000, Mathis was redshirted as a true freshman. In April 2001, he was named the Paul Crane Most Improved Offensive Lineman for Alabama along with tight end Theo Sanders. He competed with Alonzo Ephraim for the starting center job during spring practice in 2001, but lost out. Instead, he beat out Dante Ellington for the starting right tackle job, making his first start against South Carolina. Mathis started four seasons on the offensive line for the University of Alabama Crimson Tide. His first three years he played tackle, before shifting to left guard as a senior. He started 47 consecutive games beginning in the 4th game of his redshirt freshman year. 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.
Professional career
Miami Dolphins
Mathis was signed by the Miami Dolphins on September 9, 2008 after Donald Thomas, their rookie starting right guard spot was put oninjured reserve. The Dolphins released him November 8 after playing seven games for them.
Cincinnati Bengals
Mathis played for the Cincinnati Bengals from 2008–2010. He did not allow a sack during the 2009 and 2010 seasons.
Philadelphia Eagles
The Philadelphia Eagles signed Mathis to a one-year contract on July 31, 2011. Immediately after the preseason, Mathis won the starting job at left guard for the 2011 season. He signed a five-year, $25.5 million contract with the Eagles on March 17, 2012. Pro Football Focus rated Mathis as the best guard in the NFL for the 2011, 2012, and 2013 season. In 2014, he was rated as the second best guard in the league despite missing seven games due to injury. Mathis was named to the USA Today All-Pro Team after the 2012 season. Ranked #6 overall in Pro Football Focus' Top 101 of 2012. In 2013, Pro Football Focus chose Mathis for its inaugural Bruce Matthews Award recognizing the NFL's best offensive lineman. He was voted First Team All-Pro in 2013 for his excellent performance with Philadelphia. Mathis was released by the team on June 11, 2015 after he held out of OTAs in search of a new contract.
Denver Broncos
On August 25, 2015, Mathis agreed to a one-year, $2.5 million contract with the Denver Broncos. On February 7, 2016, Mathis won his first career Super Bowl when the Broncos beat the Carolina Panthers 24-10 in Super Bowl 50.
Mathis signed a one-year, $6 million contract with the Arizona Cardinals on March 16, 2016. He was placed on injured reserve on October 8, 2016 after suffering an ankle injury in Week 5 against the San Francisco 49ers. Mathis announced his retirement via Twitter on January 20, 2017.
Personal life
Mathis's uncle is Bob Baumhower, who played defensive tackle for Alabama and the Miami Dolphins. Mathis is married to his wife Katelynn, and they have 2 daughters.