Anthony Dirrell made his pro debut on January 27, 2005 against Henry Dukes. Dirrell stopped him in the first round. Dirrell had his next fight on February 11, 2005 against Dewayne Warren. Dirrell knocked Warren down twice in round one and twice again in round two. Dirrell won by TKO.
Dirrell had his third fight against Larry Brothers in which Dirrell won by TKO in the second round. Dirrell had his fourth fight against Mike Walthier knocking him out in the first round.
Dirrell had his fifth fight against Gabriel Rivera on August 13, 2005. Though Rivera was unbeaten in four fights, Dirrell won by TKO in the second. Dirrell had his sixth fight against Kevin Butts in which Dirrell knocked him out in the first round.
Dirrell had his seventh fight against Chris Grays in which Dirrell won by TKO in the first round. Dirrell had his eighth fight against Juan Carlos Ramos in which Dirrell won by TKO in the first round.
Dirrell had his ninth fight against James Morrow on June 23, 2006 in which Dirrell won by TKO in the first round. Dirrell won this fight in impressive fashion as he first knocked down Morrow with a huge right hand to the head, then followed up with a flurry in which Dirrell hit Morrow with a perfect left hook to the body which blew Morrow's mouthpiece out. Dirrell's tenth fight was against Billy Thompson in which he won by unanimous decision in 6 rounds.
On April 24, 2015 Anthony Dirrell debuted with Premier Boxing Champions vs. Badou Jack at the UIC Pavilion in Chicago, IL.
Following a 23 fight win streak, Dirrell earned the opportunity to become the mandatory challenger for the WBC Super Middleweight title. He recorded his 24th consecutive victory with a win over Renan St-Juste, when his opponent could not continue due to a shoulder injury. After another pair of wins, on December 12, 2013, Dirrell faced champion Sakio Bika at the Barclays Center in Brooklyn, New York for the title. After 12 rounds, the judges ruled the fight a draw.
On August 16, 2014, at the StubHub Center in Carson, California, Dirrell faced Bika in a championship rematch. After another 12 rounds, the judges awarded the fight and the title to Dirrell by unanimous decision.
Dirrell's next fight was on April 24, 2015 against Badou Jack at the UIC Pavilion in Chicago. Challenger Jack handed Dirrell his first full-fledged loss with a majority decision that saw the 31-year-old Swede control the fight through the middle rounds, relying on a strong jab and a confident aggression to outpoint Dirrell and win a majority decision victory.
After Badou Jack vacated the WBC super middleweight title, WBC president Mauricio Sulaiman ordered Dirrel to face Callum Smith for the vacant belt. Following Smith's entry into the World Boxing Super Series, it was announced the fight for the vacant title would be between Dirrell and David Benavidez. On August 5, the WBC announced that Dirrell would be unable to compete due to injury and the bout for the vacant world title would be between Benavidez and Ronald Gavril.
It was announced by HBO Boxing After Dark announcer Larry Merchant on the June 16, 2007 telecast that Dirrell was currently undergoing chemotherapy for non-Hodgkin's lymphoma. He was cleared to box again after completing chemotherapy in 2008.
On January 28, 2008, Dirrell was held overnight in the Flint city lockup on suspicion of armed robbery. However, no charges were ever filed. Dirrell's grandfather claims that Dirrell was on his way to undergo chemotherapy for non-Hodgkin's lymphoma when the robbery took place.