Described by many observers and fighters as stylistically "awkward",[1][2][3][4] Thompson was ranked by The Ring as the ninth best heavyweight in the world at the end of 2007 (April 2008 issue).

The brothers spent most of their youth in Southeast, D.C., frequently moving from one relative to another, before members of child and family services took them back to the orphanage.

When Tony and Keith were in first grade, they were legally adopted by their paternal grandmother and lived with her family until she died of a heart attack at the age of 54.

[9] Overall, Thompson had eight fights in 2000 and six in 2001, building up a record of 13 wins and a single decision loss, before facing his first notable opponent, Marion Wilson.

[12] On August 31, 2002, Thompson was scheduled to face hard-hitting Ron Guerrero, who was looking to regain his stock after back-to-back losses to Attila Levin and Jeremy Williams.

[16] The back-to-back wins over Guerrero and Lawrence allowed Thompson to participate in Thunderbox Heavyweight Tournament on November 30, 2002, promoted by Cedric Kushner.

[26] Thompson handed Díaz his first professional career loss, winning the bout by a wide unanimous decision, with scores 78–72, 77–73 and 79–71.

[28] The first half of the fight was competitive, with Guinn aggressively coming forward, while Thompson fought behind the jab, landing cleaner punches.

Thompson dominated the second half of the fight, patiently stalking tired Guinn and gradually accumulating the damage, hurting him on several occasions.

[28] Ibragimov was coming off of a decision loss to Calvin Brock, and viewed the Thompson bout as an opportunity to return to the heavyweight title picture.

[49] The win over Timur Ibragimov lined him up against popular German boxer Luan Krasniqi in a WBO world heavyweight title eliminator on July 14, 2007.

[28] Thompson appeared to have the upper hand from the opening bell, frequently having Krasniqi pressed against the ropes and going back-and-forth between combinations to the head and body.

Thompson agreed for a stay-busy bout on September 27, 2007, against Cliff Couser, who was coming off of an upset second-round TKO win over Monte Barrett.

[64][65] The fight took place at the Color Line Arena in Hamburg, Germany, the same venue where Thompson had defeated Luan Krasniqi in a title eliminator almost a year prior.

[63] In the middle of the eleventh, Thompson was caught with the straight right hand which he did not see coming, falling to the canvas again, with the referee starting the count this time.

[67] Despite the loss, Thompson was praised for making a solid account of himself, managing to land some punches on the dominant champion, who had seldom been hit clean by any of his opponents by that point.

[68][69] In the post-fight interview, Klitschko admitted that the fight turned out to be tougher than expected: "It is not so easy to defend all the titles and it has been a while since I last had a black eye so today I really look like a boxer.

[77][78] On April 16, 2010, Thompson faced former WBA world heavyweight title challenger Owen Beck, who was coming off of a 10th-round TKO loss to then-unbeaten Manuel Charr.

[79] The bout took place at The New Daisy Theatre in Memphis, Tennessee, after Beck's licence was revoked by several other commissions due to issues with his eyes,[80] and was aired on ESPN2 as part of the Friday Night Fights series.

[83] During his preparation, Thompson was one of the main sparring partners for then-WBA world heavyweight champion David Haye, who was training for his title defense against Audley Harrison.

[92] Thompson was then scheduled to face Eddie Chambers on 28 October 2011 in a bout televised by Showtime, for what would have been a final eliminator for IBF world heavyweight title.

"[98][99] "I've been waiting for this rematch for so long", Thompson said during one of pre-fight press-conferences, "In Berne, I'm gonna finish what I've started 4 years ago - knock Klitschko out and take the belts back to the United States".

Thompson got up but had to hold on to the ropes in order to stand, which prompted the referee to stop the fight, declaring Klitschko the winner by sixth-round TKO.

[102] In December 2012, it was announced that Thompson would fight then-highly regarded British heavyweight, ESPN's Prospect of the Year[103] David Price (15–0, 13 KOs) at the Echo Arena in Liverpool on 23 February 2013.

[105] Thompson gave David Price his first professional career loss, scoring a second-round technical knockout in front of 6,000 fans in attendance.

[114][115] Shortly after the fight it was announced that Thompson had failed a drug test and was subsequently banned by the British Boxing Board of Control for 18 months.

[117] In August, Thompson faced undefeated contender Kubrat Pulev in another IBF title eliminator, in an attempt to secure a third fight with Wladimir Klitschko.

After a competitive first seven rounds, Thompson faded down the stretch and allowed Pulev to take advantage by out-boxing him, and landing the more cleaner and effective shots.

After the bout, Thompson once again tested positive for the same substance found in his system during the Price rematch, receiving a 12-month ban from the Austrian Boxing Federation.

In March 2014, Thompson resurrected his career again after defeating 2004 Olympic gold medalist and former heavyweight title challenger Odlanier Solís by split decision.