Brewer recorded the first triple-double in University of Florida basketball history on December 18, 2005, posting 15 points, 10 rebounds and 13 assists (the 13 assists were the most by a Gator since Jason Williams had a UF-record 17 in 1997). He also drew six charges on the defensive end that game.
He was projected by ESPN.com's Chad Ford to be a lottery pick to mid-first round pick in the 2006 NBA Draft if he had entered the draft that year. However, Brewer, along with teammates Joakim Noah and Al Horford announced at the championship pep rally that they would be returning for their junior seasons. On April 5, 2007 Brewer chose to enter the NBA draft.
Brewer was selected seventh overall by the Minnesota Timberwolves in the 2007 NBA Draft. Due to the retirement of the #2 jersey in Minnesota worn by the deceased Malik Sealy, Brewer expressed the desire to sport the #22 instead. He officially adopted the #22 for the season's summer leagues, in Las Vegas, Nevada.
On December 1, 2008, it was announced that Brewer had sustained an ACL tear and would miss the rest of the 2008–09 NBA season.
Brewer at the Dallas Mavericks championship parade in 2011
On March 1, 2011, he was waived by the Knicks without playing a game for them.
On March 3, 2011, it was reported that Brewer signed a 3-year $8 million contract with the Dallas Mavericks.
On June 12, 2011 Brewer won an NBA Championship with the Dallas Mavericks as they defeated the Miami Heat 105-95 in Game 6 in Miami, though he did not play in the last game.
On December 13, 2011, it was announced that Brewer and Rudy Fernandez were traded from the Mavericks to the Denver Nuggets for a future second round draft pick.
Brewer returned to the Timberwolves on July 12, 2013, signing a reported three-year, $15 million contract.
On April 11, 2014, Brewer scored a career high 51 points in a 112-110 win over the Houston Rockets. In doing so he joined Michael Jordan, Allen Iverson and Rick Barry as the only players to record 50-plus points and 6-plus steals in one game. He also tied Kevin Love's Timberwolves' record for most points in a game.