Mason played collegiately for Tennessee State University and played professionally in Turkey, Venezuela, the Continental Basketball Association (CBA) and the United States Basketball League (USBL).
Mason attended Tennessee State University and was drafted by the Portland Trail Blazers in the third round of the 1988 NBA draft (53rd pick), but was cut shortly afterwards.
He then played for the Efes Pilsen basketball club in Turkey.
Mason played for Marinos de Oriente in Venezuela and other teams in the CBA and the USBL for about a year.
He had brief stints with the New Jersey Nets, where he averaged 1.8 points.
He also played for the Denver Nuggets, where he played only 3 games.
In 1991, Mason played as a power forward for the United States Basketball League team the Long Island Surf. In his one season with the Surf, Mason was named to the All-USBL First Team, averaging more 27.8 points and 11.2 rebounds per game, and he set a league record with 28 rebounds in a game. Ed Krinsky, general manager of the Surf, said, "I really believed he could play in the N.B.A. He was a huge guy with backcourt skills," and later that year, Mason was already on the New York Knicks' summer league roster, with Pat Riley as coach. In the year 2000, in celebration of the USBL's 15th anniversary, USBL fans voted put together the "All-15 Team," meaning the best all-time best USBL players from 1985 to 2000, many of whom went on to become renowned NBA stars, and Mason was one of those 15.
Mason then signed with the New York Knicks in the summer of 1991. In the 1990–91 season, Mason played 26 games for the CBA's Tulsa Fast Breakers, with whom he averaged 29.9 points and 14.8 rebounds per game in his only season in the league.
Under coach Pat Riley, Mason blossomed in New York, where he made up a strong front court alongside Patrick Ewing, Charles Oakley and Charles Smith. In 1994, the Knicks reached the NBA Finals for the first time since 1973 but lost in seven games to the Hakeem Olajuwon-led Houston Rockets. Mason was traded in 1996 to the Charlotte Hornets with Brad Lohaus for Larry Johnson. In 2000, he was sent to the Miami Heat with Eddie Jones, Ricky Davis and Dale Ellis for Jamal Mashburn, P.J. Brown, Tim James, Rodney Buford and Otis Thorpe, and finished his career with the Milwaukee Bucks. He retired in 2003, and fixed residence in Memphis, Tennessee.
Mason won the NBA Sixth Man of the Year award in 1995. He was named to the 1996-97 All-NBA Third Team and to the NBA All-Defensive Second Team. He led the league in minutes played in 1995-96 (3,457), also setting a Knicks record with the number. He also led the league in minutes played per game in 1996–97 (43.1).
His first season with the Hornets was the best in his NBA career. He recorded career-highs in minutes played (43.1), points (16.2), rebounds (11.4) and assists (5.7) and also 4 triple-doubles (the first in his career). He missed the entire 1998-99 season due to a ruptured biceps injury , then averaged 11.6 points and 8.5 rebounds the following one.
In Miami, although Mason had been brought over by Miami coach Pat Riley to be a role player on what was thought to have been a contender Heat team, the kidney ailment of Alonzo Mourning forced Mourning to sit out and made Mason a starter for the team. Mason would respond by finishing second on the team in scoring with 16.1 points per game and average 9.6 rebounds. With Mourning and Grant Hill selected but unable to play due to injury in the 2001 NBA All Star Game, Mason was chosen to represent the Heat in his only selection to an All-Star team. Mason helped the Heat make the playoffs with a 50 win season for the injury ravaged Heat. Mason however virtually disappeared in the playoffs, taking only 13 shots and averaging a mere 5.3 points and 3 rebounds in three games. Mason was waived during the offseason.
He signed with the Milwaukee Bucks for the 2001–02 season. In Mason's first season with the Bucks, the team stumbled to a 41-41 record (11 games worse than the previous season) and missed the playoffs altogether. Mason's numbers went down as well: 9.6 ppg, 7.9 rpg. Nonetheless Milwaukee stuck with Mason for another year, waiving him after the 2002–2003 season.
Mason's son Anthony Mason Jr. played on the St. John's University Red Storm basketball team. He completed his eligibility for the 2009–10 St. John's Red Storm, and he went on to try out with the Miami Heat, before playing for teams such as the Sioux Falls Skyforce and Cholet Basket. Another son, Antoine, played basketball at Auburn University after transferring there from Niagara University, where he led the 2012–13 Niagara Purple Eagles in scoring as a redshirt sophomore. Antoine was also the second leading scorer in the NCAA as a redshirt junior (only behind Creighton's Doug McDermott).
Mason and his former girlfriend are allegedly the subject of the song "I Got a Story to Tell" by The Notorious B.I.G.. In the song, B.I.G. describes a situation in which he was sleeping with another man's girlfriend at that man's house. When the man returns unexpectedly, B.I.G. tied up the girlfriend, then drew a gun on the man and demanded money. He obeyed and B.I.G. left to share this story with his friends. Although B.I.G. never named Mason, he did mention "a player from the New York Knicks" as the girl's boyfriend and that this player's height was 6 feet 5 inches (1.96 m). On May 16, 2016, Fat Joe claimed that "I Got a Story to Tell" was about Mason on the ESPN show Highly Questionable, saying it is a "very strong possibility, rumor" the song is about Mason. Since he died before the reveal, Mason could not comment to confirm whether or not the song is about him. Former teammate John Starks also appeared on Highly Questionable prior to Mason's death in 2015 and was also asked about who "I Got a Story to Tell" was about. Starks said he knew that the events described in the song really happened, but declined to reveal a possible name.
Mason suffered a massive heart attack in early February 2015 and was diagnosed with congestive heart failure. He later succumbed to the condition, and died on February 28, 2015, in Manhattan at the age of 48.
In the TV series New York Undercover, Mason appeared in two different episodes, playing himself in one. He also plays a pickup player in the 1996 film Eddie, and himself in Woody Allen's Celebrity.
In addition, Mason appears in the Diamond D rap video "Best Kept Secret", dunking his way through the video on a New York City playground basketball court.
The Beastie Boys song "B-Boys Makin' With The Freak Freak" from 1994's "Ill Communication" LP mentions him with the lyric "I got my hair cut correct like Anthony Mason" – the Beasties being NY Knicks fans.
He also appeared in the Beastie Boys music video "Root Down".