He played in the NBA for the Utah Jazz, Toronto Raptors, Dallas Mavericks, New Jersey / Brooklyn Nets, Boston Celtics, Washington Wizards, Phoenix Suns, and the Atlanta Hawks from 2004 to 2016.

Humphries attended Hopkins High School, where he led the team to a 25–2 record in 2002 and its first Minnesota state championship in 49 years.

He averaged 21.7 points and 10.1 rebounds (both tops in the Big Ten), while shooting .444 percent from the field and .742 from the line.

[8] Critics accused Humphries of playing selfishly, preferring to inflate his statistics and NBA draft stock rather than help the team win games.

[17][18] Humphries concluded his inaugural season with the Raptors with a career-high 3.1 rpg and .470 field goal percentage, as well as 3.8 ppg.

[19] On January 11, 2010, the Mavericks traded Humphries along with G/F Shawne Williams to the New Jersey Nets in order to re-acquire Eduardo Nájera.

[22] On June 27, 2013, ESPN.com reported that the Nets and Boston Celtics had worked out a trade that would send Humphries and four other players (Keith Bogans, MarShon Brooks, Kris Joseph, and Gerald Wallace) as well as three future first-round draft picks to Boston in exchange for Kevin Garnett, Paul Pierce, and Jason Terry as well as D. J.

[24] On July 19, 2014, Humphries was acquired by the Washington Wizards in a sign-and-trade deal that sent a protected 2015 second round pick and a trade exception to the Boston Celtics.

[25] On October 9, 2014, he underwent successful surgery to repair nerve damage in his right small finger, and was subsequently sidelined for three to four weeks.

[26] On November 14, 2015, Humphries made 5-of-8 three-pointers on his way to a game-high 23 points, helping the Wizards defeat the Orlando Magic 108–99.

[27] On February 18, 2016, Humphries was traded, along with DeJuan Blair and a 2016 protected first round draft pick, to the Phoenix Suns in exchange for Markieff Morris.

[31] Three days later, he made his debut for the Hawks in a 106–77 win over the Los Angeles Lakers, recording 14 points, eight rebounds, one steal and one block in 22 minutes off the bench.

Junior World Championship Qualifying Tournament Team, alongside future Raptors teammate Chris Bosh.

[5] The team finished with a 4–1 record and the bronze medal and qualified for a berth in the 2003 FIBA Junior World Championship.

[40][41] On December 1, 2011, Humphries filed his response to Kardashian's petition, requesting an annulment on the grounds of fraud or a decree of legal separation rather than the Kardashian-requested divorce.