In a 13-year NBA career, Van Exel played for the San Antonio Spurs, Portland Trail Blazers, Golden State Warriors, Dallas Mavericks, Denver Nuggets, and Los Angeles Lakers.
Van Exel's career began when he was selected by the Los Angeles Lakers in the second round as the 37th overall pick of the 1993 NBA draft. Van Exel and Eddie Jones were the centerpieces of the Lakers' rebuilding plan after the end of their successful Showtime era in the early '90s. Led by Van Exel's flashy play, the two guards helped the team to the playoffs in 1995 after the Lakers had missed the postseason for the first time in years in 1994. Van Exel was known for his shooting streaks, buzzer-beating shots, and speed, earning him the nickname "Nick the Quick".
During his career with the Lakers, Van Exel averaged 14.9 points per game as well as 7.3 assists per game, finishing in the top 10 in the NBA in that category twice. On June 24, 1998, after five seasons as the starting point guard, Van Exel was traded to the Denver Nuggets for Tony Battie and the draft rights to Tyronn Lue. Playing on a Nuggets team which was one of the worst in the league, Van Exel achieved several career highs. Over four seasons he put up averages of 17.7 ppg and 8.4 apg, averaging 21.4 ppg through 45 games of the 2001–02 season.
Due to knee and elbow injuries, he only played in 65 games during the 2005–06 season with the San Antonio Spurs. He averaged career lows in almost every statistical category, including points (5.5 ppg) and minutes (15 mpg). In the playoffs, San Antonio was eliminated by the Dallas Mavericks in a series that lasted seven games. Two days later, on May 24, 2006, ESPN's Tony Kornheiser and Michael Wilbon reported on their show Pardon the Interruption that Van Exel would soon announce his retirement.
Van Exel was famous throughout his playing career for his peculiar free-throw routine, in which he took his free throw attempts while standing well over a foot behind the free-throw line. Also, he is known as one of the most popular left-handed players in history.
Today Van Exel is working as an assistant coach of the Memphis Grizzlies.