After short stints with the Boston Celtics, Dallas Mavericks, and San Antonio Spurs and becoming a free agent in June 2017, Lee retired in November 2017.

Lee's senior year, he was joined by incoming freshmen and future NBA players Al Horford, Corey Brewer, Taurean Green, and Joakim Noah.

Lee posted 23 points on 10–11 shooting, along with 15 rebounds and three steals in 52 minutes as the Knicks went on to defeat the Phoenix Suns in triple-overtime on January 2, 2006.

On December 20, 2006, in a double-overtime game against the Charlotte Bobcats with 0.1 seconds left, Lee scored the winning basket by tipping in an inbound pass.

This was within the league's so-called Trent Tucker Rule, whereby a player cannot catch and shoot a successful field goal with less than three-tenths of a second remaining on the clock.

At the All-Star break, Lee had averaged 11.1 points on 61% shooting (first in the league), an 80% free throw percentage, 10.8 rebounds (8th in NBA) and 1.8 assists in 30.9 minutes a game.

On February 16, 2007, Lee, playing for the Sophomores, was named the Most Valuable Player in the Rookie Challenge, finishing with 30 points on 14 of 14 shooting from the field and 11 rebounds.

On February 23, 2007, in a game against the Milwaukee Bucks, Lee came down on future teammate Andrew Bogut's foot and sprained his ankle.

[10] On February 11, 2010, Lee was chosen to replace an injured Allen Iverson on the East team at the 2010 NBA All-Star Game.

[11] On April 2, Lee recorded the first triple-double of his career, putting up 37 points, 20 rebounds, and 10 assists against the Golden State Warriors.

On July 9, he was signed and traded to the Golden State Warriors, who sent Anthony Randolph, Kelenna Azubuike, Ronny Turiaf, and a future second-round pick to the Knicks.

On February 7, 2012, Lee recorded his second triple-double, scoring 25 points and getting 11 rebounds, and 10 assists in a loss against the Oklahoma City Thunder.

[16] Despite the injury, which was expected to end his season, Lee returned for the sixth and final game of the series as the Warriors upset the Nuggets.

On July 27, 2015, Lee was traded to the Boston Celtics in exchange for Gerald Wallace and Chris Babb,[22] as Golden State was seeking to offload his salary given his limited role on the team.

[28] In his second game for the Mavericks on February 26, he recorded 14 points and 14 rebounds in 25 minutes off the bench in a 122–116 overtime win over the Denver Nuggets.

[29] On March 25, Lee returned to Oracle Arena for the first time since being traded from the Warriors and got a standing ovation during a pre-game ceremony in which he received his 2015 championship ring.

[32] He made his debut for the Spurs in their season opener on October 25, 2016, recording six points, six rebounds, and two assists in 11 minutes off the bench in a 129–100 win over his former team, the Golden State Warriors.

[35] In 2007 Lee appeared on the game show Family Feud, in an NBA Players vs Mothers week, to raise money for charity.