Mathis was born in Gainesville, Texas, and attended Gainesville High School. He was a letterman in football, basketball, and track. In football, he was a two-time All-District selection.
He played college football at Texas A&M University-Commerce, becoming a three-year starter at cornerback, while finishing with 16 interceptions and three NCAA Division II All-American and All-LSC nominations.
In 2009, he was inducted into the Texas A&M-Commerce Athletic Hall of Fame.
Mathis wasn't selected in the 1997 NFL Draft because of his size and small college background. He was signed by the Dallas Cowboys as an undrafted free agent. He would end up making the team after taking advantage of Deion Sanders being away while playing professional baseball and displaying his track speed (4.19 seconds in the 40-yard dash). As a rookie, he played in all 16 games, returned punts and recorded 12 special teams tackles.
After being the backup at right cornerback, he was moved to the left side to backup Kevin Smith. At the end of the 1998 season he won the starting job from an injured Smith, but he would also miss time because of injuries (8 games in 1999) and returned to a backup role.
In 2000, the Cowboys had a lot of turnover at linebacker and one of the moves made to improve the depth was trading Mathis to the New Orleans Saints in exchange for linebacker Chris Bordano on April 26. Also factoring in the decision was his injury history and the numbers at the cornerback position (signing of Ryan McNeil and 3 rookie cornerbacks draft selections).
Mathis was named the starter at left cornerback for all 16 games in the 2000 season and finished with 87 tackles and 1 interception. He helped the New Orleans Saints reach the playoffs for the first time since 1992 and also win their first ever playoff game.
As a starter in the 2001 season, he injured his cervical spine while tackling the Washington Redskins' Ki-Jana Carter. On July 24, 2002, he was waived injured.
Mathis recovered and played 11 games in the nickel packages for the Atlanta Falcons in 2002, registering a career-high 3 interceptions. He started 12 games in 2004, finishing with 67 tackles and 2 interceptions (both returned for touchdowns).
On September 13, 2005, he was lost for the season with a career-threatening left knee injury, after tearing 3 ligaments during a practice drill.
The next year, he returned to play but suffered a career-ending neck injury, while tackling Eddie Drummond on the opening kickoff against the Detroit Lions on November 5, 2006. He was released injured on April 9, 2007.
In 2012, he became a football assistant coach at Prime Prep Academy.