He was selected by the Tennessee Oilers in the fourth round of the 1997 NFL draft after playing college football for the Michigan State Spartans.

Following eight seasons with the Oilers franchise (which was renamed the Titans in 1999), including two Pro Bowl selections (2000 and 2003), Mason signed with the Baltimore Ravens in 2005.

The following season, he again played in all 16 games and this time recording 25 catches for 333 yards and three touchdowns, the first of his career came versus the Chicago Bears on October 25.

He also returned a kickoff 80 yards for a touchdown in the Titans 33–14 win over the Jacksonville Jaguars in the AFC title game.

In 2003, he started all 16 games and finished the season with 1,303 receiving yards and 95 receptions which was the 5th highest in the NFL.

Mason dislocated his shoulder when he fell after a catch in a game against the Houston Texans, eventually coming back to finish the contest.

[7] Mason re-aggravated of his injury against the Dallas Cowboys,[8] but finished the game with six catches for 66 yards and one touchdown.

Some said that Mason was a cancer to the team, and that he complained about offensive coordinator Brian Schottenheimer's playcalling.

Said Mason, "I never complained to Rex Ryan or Mike Tannenbaum, and I hope that one day it come out who actually did it, but I doubt it."

"[13] The Jets traded Mason to the Houston Texans on October 11, 2011, in exchange for a conditional seventh-round draft pick.

Mason announced his retirement from professional football by signing a 1-day contract with Baltimore Ravens on June 11, 2012.

[15] As of 2019[update]'s NFL off-season, Derrick Mason held at least 26 Titans franchise records, including: Mason and his wife, Marci, were married on June 7, 1997, and have a daughter, Bailee My-Lin and a son, Derrick James II.

Mason is currently an afternoon radio host for 102.5 The Game, a sports station based in Nashville.