On June 28, 2007, Oden was selected first overall in the 2007 NBA draft by the Portland Trail Blazers. He underwent microfracture surgery of the knee in September 2007, and missed the entire 2007–08 NBA season as a result. He recovered and made his NBA debut on opening night 2008. On March 15, 2012, he was waived from the Trail Blazers after a long history of injuries. He signed with the Miami Heat on August 7, 2013, more than three years after last appearing in an NBA game. On October 28, 2016, Oden stated that he was done with basketball and will not be returning as a player.
Oden was born in Buffalo, New York, and moved with his family to Terre Haute, Indiana at the age of nine. He attended Sarah Scott Middle School in Terre Haute, where he first played interscholastic basketball. Oden then relocated with his mother and brother and attended Lawrence North High School in Indianapolis, Indiana which he led to three consecutive Indiana Class 4A basketball championships before graduating in 2006. He was named Parade's High School Co-Player of the Year 2005 (along with Monta Ellis) and 2005 National Boys Basketball Player of the Year. He repeated as Gatorade National Boys Basketball Player of the Year in 2006. Oden was named the 2006 Indiana Mr. Basketball. He was also on the McDonald's All-American Team and played in the All-American game, and earned first-team Parade All-American honors for the second straight year.
On June 29, 2005, Oden and Lawrence North teammate Mike Conley, Jr. announced that they would be attending Ohio State University starting with the 2006–07 season.
Oden had surgery on his right wrist on June 16, 2006, in Indianapolis to repair a ligament injury that occurred late in his senior high school season. As a result, he sat on the Ohio State bench during the beginning of the 2006–07 season, during which the Buckeyes were ranked as high as #1 before losing to North Carolina. He made his college debut on December 2, 2006, against Valparaiso, coming off the bench. He finished the game with 14 points, 10 rebounds and 5 blocks. In December of that year, Steve Kerr described him as a "once-in-a-decade player".
The Big Ten honored Oden as Player of the Week, along with Wisconsin's Alando Tucker, on January 29, 2007. In the previous week, he had averaged 18 points and 11.5 rebounds. On March 6, 2007, Oden was named First Team All-Big Ten as well being voted the conference's Defensive Player of the Year. Oden fouled out for the first time in his college career against Xavier in the second round of the NCAA Tournament, and was bothered by foul trouble throughout the tournament. In the Sweet Sixteen, Oden blocked a potential game-winning shot in the final seconds against Tennessee to preserve an 85–84 victory, and went on to lead Ohio State past Memphis and Georgetown to advance to the 2007 National Championship. In the title game, Oden scored 25 points, and had 12 rebounds and 4 blocked shots in a losing effort against the Florida Gators.
Oden, alongside Kevin Durant, Arron Afflalo, Alando Tucker and Acie Law were named to the Associated Press All-American Team. Oden and Durant were the first freshmen voted to the All-American First Team since 1990, and the third and fourth overall. Throughout his high school and college career, Oden never lost a home game.
On April 20, 2007, Oden announced that he would be entering the 2007 NBA draft. On June 28, 2007, he was selected by the Portland Trail Blazers with the #1 overall pick. To begin his Trail Blazers career, Oden chose the uniform number 52. On July 1, before his first NBA practice, Oden was signed to a contract which provided for two guaranteed seasons and team options for third and fourth seasons. On September 14, 2007, Oden had microfracture surgery on his ailing right knee. He missed the entire season. Oden's progress was recorded on the Trail Blazers' website and his blog.
Although drafted in 2007, Oden was classified as a rookie for the 2008–09 season because of the knee injury. Entering the 2008–09 season, he was listed at 250 lb (110 kg), but according to Blazers' trainer Jay Jensen he weighed about 290 lb (130 kg) in July. Oden left his NBA debut with a foot injury after playing thirteen scoreless minutes against the Los Angeles Lakers. He returned on November 12, 2008, after missing two weeks, and scored his first NBA points in the first quarter against the Miami Heat. On January 19, 2009, Oden had a career-high 24 points while also grabbing 15 rebounds in a 102–85 win against the Milwaukee Bucks. On February 13, 2009, he injured his left knee in a game against the Golden State Warriors, by bumping knees with opponent Corey Maggette, and missed three weeks due to a chipped knee cap.
On November 23, 2009, Oden matched his career-high for points in a game again with 24. He set a new career-high for rebounds in a game with 20 on December 1. On December 5, 2009, Oden injured his left knee in the first quarter of a game. He was taken off the court on two connected stretchers. Later, he underwent surgery for a fractured left patella and missed the rest of the season. That injury marked the second time Oden had missed major playing time due to injury.
On November 17, 2010, the team announced that Oden would have microfracture surgery on his left knee, ending his 2010–2011 season. The injury marked Oden's third NBA season cut short due to a knee injury.
On December 9, 2011, the Trail Blazers announced that Oden had suffered an unspecified "setback" that left them less optimistic about his ability to play in the 2011–2012 season. Rather than signing an 8.9-million-dollar qualifying offer, Oden and the team negotiated a different offer. On February 3, 2012, Oden underwent arthroscopic surgery on his right knee. On February 20, 2012, Oden was scheduled for a procedure on his left knee similar to the procedure he underwent 17 days earlier. However, during the operation, further damage to the articular cartilage was discovered, and Oden underwent his third micro-fracture surgery.
On March 15, 2012, Oden was waived by the Trail Blazers to create room on the roster for trade acquisitions. In May 2012, Oden announced his intention to sit out the 2012–13 season to focus on rehabbing his injuries. In January 2013, it was reported that several teams were interested in signing Oden for the 2013–14 season.
On August 7, 2013, Oden signed a one-year deal with the Miami Heat. He played in his first NBA game since December 5, 2009 in a preseason game against the New Orleans Pelicans on October 23, 2013. He managed to score two points through a dunk attempt and grabbed two rebounds in four minutes of play.
On January 15, 2014, Oden made his long-awaited return to the court. In his first regular season game since December 2009, he recorded 6 points and 2 rebounds in 8 minutes of game time in a 114–97 loss to the Washington Wizards. On February 23, 2014, Oden made his first start since December 2009 in the Heat's 93–79 win over the Chicago Bulls. The Heat made the 2014 NBA Finals where they faced the San Antonio Spurs. They went on to lose the series in five games.
In March 2015, Oden was reported to be working out with the Memphis Grizzlies, while he also returned to his alma mater, Ohio State, to undergo some "high-level training" with Thad Matta, the Ohio State basketball team coach. Matta stated that since September 2014, Oden had been working out with the other Ohio State coaches. In June 2015, Oden had workouts with the Charlotte Hornets and the Dallas Mavericks. He told the media that he was attempting an NBA comeback with plans to return to the league for the 2016–17 season.
On August 26, 2015, Oden signed a one-year, $1.2 million contract with the Jiangsu Dragons of the Chinese Basketball Association. On December 9, he recorded a season-high 22 points and 14 rebounds in a win over Shandong. On February 1, 2016, he parted ways with Jiangsu. In 25 games for the club, he averaged 13.0 points, 12.6 rebounds and 2.0 blocks per game.
On August 11, 2014, Oden was charged with battery for allegedly punching his ex-girlfriend in the face on August 7 in Lawrence, Indiana. He pleaded guilty in 2015 to battery with moderate bodily injury, and the other three charges were dropped. He was put on probation and ordered to pay a fine and attend counseling.
On April 12, 2016, Oden was hired by the Ohio State Buckeyes men's basketball team to be the student manager for the team while he goes back to finish his degree at the college. Despite becoming a manager at the school, Oden is reportedly still waiting to be offered a contract by any basketball team overseas in order to continue his basketball career, but when asked in October if he'd play basketball again, he said, "I wish. It's over."