Odom was selected fourth overall in the 1999 NBA draft by the Los Angeles Clippers. He made his NBA debut on November 3, 1999 and managed just two minutes against the Boston Celtics before leaving with an injury. In 2000, Odom won the NBA’s Sixth Man of The Year Award as a member of the Clippers. His tenure with the Clippers ended midway through the 2001–02 season when he was traded, along with Brian Skinner and Caron Butler, to the Miami Heat in exchange for Jamal Mashburn, Jason Williams and James Posey. Odom spent one season with the Heat before becoming a free agent at the end of that 2002-03 season.

Odom’s journey to the Lakers began during the summer of 2003, when that year’s free-agent class first gathered as teams and players started negotiating contracts that would shape their futures.

Odom was one of many players who were contacted by the Lakers about their interest in signing him. Former Lakers star Kobe Bryant told Odom the team would love to have him, but that it wasn’t likely they could afford his signing, given their salary cap situation at that time.

Odom eventually signed with the Miami Heat for one year at $3.5 million after talks between his representatives and the Clippers broke down. The Heat were allowing him to become a free agent again at the end of the year.

The Lakers traded Caron Butler and Chucky Atkins in a package that landed them Lamar Odom, Brian Grant and a second-round draft choice from the Heat in exchange for drafting Derek Fisher. The Lakers’ moves enabled Odom’s re-signing with Los Angeles on August 3, 2004.

Odom helped the Lakers to three consecutive NBA Finals appearances (2008, 2009 and 2010), winning back-to-back championships over the Orlando Magic in 2009 and Boston Celtics in 2010.

Odom was traded to the Dallas Mavericks on December 11, 2011 in a multi-player deal that included the Lakers’ Lamar Odom and the Mavericks’ Caron Butler and Shawn Marion. The Mavericks viewed Odom as an important piece for their title hopes that season. However, he did not see eye-to-eye with coach Rick Carlisle, who at one point called Odom a “mole” for the team’s group of older players.

Odom was eventually waived by Dallas late in January 2012 after refusing to accept a D-League assignment with the Texas Legends. He had appeared in only 12 games for the Mavericks, averaging 6 points and 4 rebounds in 19 minutes per game. Mavericks owner Mark Cuban admitted that a clash between the two during halftime in a game against the Memphis Grizzlies on April 7 was the last straw. Odom reportedly responded angrily when Cuban questioned his commitment, asking if he was “in or out.

On June 29, 2012, Odom was traded back to the Los Angeles Clippers as part of a four-team deal. He played all 82 games of the season for the third time in his career, but only started two of them.

On August 11, 2014, Odom signed a contract with Laboral Kutxa of the Liga ACB and Euroleague. He left the team in December without appearing in a game for them due to back problems, and joined Spanish side Baskonia later that month.