Anderson left school and entered the NBA draft in 1989, where he was selected with the eleventh pick of the first round by the Orlando Magic. As the Magic were an expansion team that season, Anderson was the first draft pick in the franchise's history.
Like most expansion franchises, the Magic were a young team and Anderson was one of its few bright spots. As a result, the Magic were awarded high draft picks in several consecutive years, including Dennis Scott in 1990, Shaquille O'Neal in 1992, and Chris Webber, who was traded for a package including Penny Hardaway in 1993. In his first few seasons, Anderson was the Magic's top scoring option, and led the team in points per game during the 1991–92 season. As the team's talent level increased, Anderson was gradually relegated to a lesser offensive role but remained a consistent member of the team's starting lineup. Exceptions include the April 23, 1993, game at New Jersey, in which he scored a career-high 50 points off the bench. In 1994–95, Anderson led Orlando in three-pointers with 179, and averaged 15.9 points per game. The Magic won 57 games, finished with the best record in the Eastern Conference, and won their first ever Atlantic Division title.
In the Eastern Conference semifinals, the Magic faced the Chicago Bulls and Michael Jordan, who had recently returned from an aborted baseball career wearing the number 45 instead of his famous number 23. At the end of Game One, Anderson famously stripped Jordan from behind, leading to the game-winning basket for the Magic. He later commented that Jordan "didn't look like the old Michael Jordan" and that "No. 45 doesn't explode like No. 23 used to." Jordan then returned to wearing his old number in the next game, scoring 38 points in a Bulls win.
Game One of the NBA Finals was against the defending champion Houston Rockets, at the Orlando Arena. With the Magic up by three points late in the game, Anderson, typically a 70% free throw shooter, missed four consecutive free throws that could have sealed the victory for Orlando. Kenny Smith hit a three-pointer for Houston shortly thereafter, tying the game and sending it to overtime. The Rockets went on to win the game in overtime and eventually swept the Magic, winning their second consecutive NBA Championship. As a result of this incident, some Orlando fans began to label Anderson with the derogatory nicknames of "Nick the Brick" and "Brick Anderson."
Two seasons after the 1995 finals, Anderson's career took an abrupt downward spiral, largely due to a sudden inability to shoot free throws, and he even suffered an injury in Game 3 of the 1996 conference finals in a rematch against the Bulls and was out for the season. During the 1996–97 season, Anderson's free throw shooting percentage tumbled to a career-low 40.4% and his scoring average to 12.0 points per game. Anderson had to be removed from the closing minutes of several close games due to being undependable at the charity stripe.
His struggles worsened through the first half of the 1997–98 season. Through January 27 of that season, Anderson was averaging only 6.5 points per game, and shooting a paltry 36.3% from the free throw line. However, in the second half of the season, Anderson experienced a sudden career revival, as his scoring average abruptly jumped to 22.6 points per game, and his free throw percentage improved to a 67.6%, a figure close to his former career average. He ended the season with a scoring average of 15.3 points per game.
Anderson would play on with the Magic through the lockout-shortened 1998–99 season, after which he was traded to the Sacramento Kings. He left Orlando as the team's career scoring leader. He was the last player remaining from the Magic's original expansion roster, having remained with the franchise for ten seasons.
He played two seasons in Sacramento, averaging a career-low at that point, 10.8 points per contest in 72 games his first season. He played 21 games the next season, and 15 games in his final season, in which he played for the Memphis Grizzlies.
Anderson works for the Orlando Magic in the team's community relations department. He also serves as a commentator for Fox Sports Florida during the Magic's pre-game, halftime and post-game shows.