Whyte was born in Port Antonio, Portland, Jamaica, on 11 April 1988. In the 1990s, Whyte moved with his family to the United Kingdom at 12 years of age. His paternal grandfather was an Irishman named Patrick Whyte, who emigrated to Jamaica from Dublin, Ireland. Of his early life Whyte has spoken of performance in academia at school in England, while adding: “I had no schooling at all when I lived in Jamaica.” As Whyte mentioned on iFL TV numerous times, it was hard times growing up in Jamaica, where he was “dodging bullets” and around situations no child at such an age should. Whyte grew up in Brixton, London and fought at Miguel’s Boxing Gym. He had spoken of the influencing experience boxing has had upon his early life, by stating: “I didn’t do too well at school, to be honest, but boxing saved me and changed my life. And it was going well, because I knew it was my best chance in life.”

Originally, Whyte was a professional kickboxer, to which he became two-time British heavyweight kickboxing champion by claiming the BIKMA super-heavyweight British title, and one-time European K1 champion, while being ranked UK #1 for five years in his weight category of 95 kg +, ending his kickboxing career with a K-1 record of 20–1, before then turning to MMA. Whyte made his professional MMA debut on 6 December 2008, at the Ultimate Challenge MMA, on the James McSweeney vs. Neil Grove undercard, where he defeated Mark Stroud with a hugely destructive right cross only 12 seconds into the round; ultimately winning by knockout (KO) at The Troxy.

In his first amateur bout, in 2009, aged 20, Whyte beat Anthony Joshua by unanimous decision (UD) over three rounds. He had stated prior to the fight that his trainer Chris Okoh admitted that the decision to agree to the fight was then considered a risk, albeit ultimately accepting the fight to which Whyte had stated, “But I said I’d take it. Sometimes you’ve just got to take opportunities when they come.”

Whyte had a limited amateur record (6–0–0, 5 KOs) because of a dispute with the ABA regarding his kickboxing background, which led him to turn professional in 2011, although trainer Okoh wanted him to remain amateur. Whyte signed with boxing promoter Frank Maloney, after friends of Maloney witnessed sparring sessions Whyte had with David Haye and former UFC light-heavyweight champion Quinton Jackson.

Whyte made his professional debut on 13 May 2011. He fought Tayar Mehmed and won via points decision (PTS) in the fourth round, obtaining the decision of 40–36. On 16 September 2011, Whyte made his second professional appearance against his Lithuanian heavyweight journeyman opponent Remigijus Ziausys. Whyte ultimately won by PTS in the fourth round, obtaining the decision of 40–37.

On 3 December 2011 Whyte defeated Croatian Toni Visic, winning by technical knockout (TKO) in the third round due to referee Jeff Hinds stopping the fight at 1 minute 46 seconds.

The next fight for Whyte was against veteran journeyman Hastings Rasani on 21 January 2012 at the Liverpool Olympia in Liverpool. Whyte scored a PTS win based over Rasani, making it his third win on points.

For his fifth professional bout, Whyte defeated Bulgarian Kristian Kirilov by TKO in the first round at The Troxy, Limehouse on 2 March 2012, which was followed by an additional TKO in his sixth bout in the first round on 19 May 2012 against Georgian Zurab Noniashvili at the Aintree Racecourse, Liverpool. Whyte went on to fight Hungarian giant Gabor Farkas at the York Hall in London on 7 July 2012, winning by second-round KO; it marked the first KO victory in Whyte’s professional career.

Two months later on 15 September 2012, Whyte challenged former British heavyweight champion Mike Holden to a bout scheduled for six rounds. Holden was put down once in the second and twice in the third round, to which referee Jeff Hinds stopped the fight. Whyte’s last fight of 2012 was against Sandor Balogh, which took place in Bluewater, Greenhithe, Kent on the James DeGale undercard when DeGale fought Hadiliah Mohoumadi for the European super-middleweight title on 13 October 2012. Whyte won the bout but was later stripped of the win due to testing positive for banned substances.

Whyte was cleared to compete from 12 October 2014, since his two-year ban by UKAD and returned to boxing on 21 November 2014 at the Camden Centre in London to fight Ante Verunica, a fight which lasted all of two rounds as Whyte delivered a hard shot that forced a stoppage from referee Jeff Hindsfor a TKO victory. On 28 November, one week after his fight with Verunica, Whyte returned to the Camden Centre and put on another dominating display stopping Tomas Mrazek, with Whyte knocking the durable Mrazek down three times in the third round.

On 20 December 2014, Whyte scored another TKO win, this time over heavyweight hope Kamil Sokolowski in three rounds at the City Hall in Hull.

Whyte followed up his Sokolowski win with a KO victory over Marcelo Luiz Nascimento on 7 February 2015 at the Camden Centre to which the Brazilian had never been stopped as quickly in his career.

On 1 August 2015, Whyte faced Irineu Beato Costa Junior, at the KC Lightstream Stadium in Hull, on the undercard of Rumble on the Humber featuring Luke Campbell’s clash against Tommy Coyle in a WBC lightweight eliminator. Whyte sent the Brazilian crashing backwards to the canvas, and referee Michael Alexander stopped the fight with 2 minutes 41 seconds remaining in the first round as Whyte put Costa back to the floor with a right hand.

On 14 September 2015, it was announced that Whyte would fight old rival Anthony Joshua for the vacant British heavyweight title on 12 December at The O2 Arena in London on Sky Sports Box Office. Joshua was able to use his power to hurt Whyte in the first round. He appeared hurt again in the second round but was able to catch Joshua with a counterpunch and follow it up, leaving Joshua visibly shaken. Whyte also landed several body shots towards the end of the round. This continued somewhat in the third round with Joshua still looking tired and stiff legged. As the rounds went on, Joshua regained his composure and took control. Whyte took many hard shots before coming back with his own, his chin has since been lauded by critics. Whyte was rocked again in the seventh round from a heavy right hand to the temple. Joshua was able to follow through and landed an uppercut that put Whyte down through the ropes and knocked him out.

Following the loss to Joshua, Whyte spent some time recovering from a shoulder surgery and returned to the boxing ring on Joshua’s first world title defence at The O2 Arena on 25 June 2016. Prior to the fight, Whyte signed a deal with Matchroom Sport. Whyte defeated Ivica Bacurin via KO. Whyte started off slow, before working on the jab and knocking Bacurin out with a right hand.

In April 2017 it was announced that Whyte would headline a card at The O2 Arena on 3 June 2017. Whyte listed Bryant Jennings, Mariusz Wach, Artur Szpilka and Gerald Washington as potential opponents. On 14 April, Washington put his name forward wanting to get back into the world title mix following his failed attempt to dethrone WBC heavyweight champion Deontay Wilder in February 2017. On 19 April, Matchroom Boxing revealed Whyte’s opponent would be 37 year old former world title challenger Mariusz Wach (33–2, 17 KOs). The fight was to take place live on Sky Sports and would also feature younger talents including Reece Bellotti, Ted Cheeseman and Lawrence Okolie. The fight was postponed on 16 May due to Whyte injuring his foot. There was no immediate mention as to when the fight would be rescheduled for.

In early June, promoter Eddie Hearn of Matchroom Boxing confirmed that Whyte would be making his US debut in the Summer of 2017 in order to earn himself a potential world title shot by the end of the year. On 25 July, Hearn announced that Whyte would fight 44 year old former world title challenger Michael Grant (48–7, 36 KOs), who was on a three fight losing streak since 2013. Grant had only fought once since October 2014, which took place in April 2017 in a KO loss to Krzysztof Zimnoch. Grant unsuccessfully challenged then unified heavyweight champion Lennox Lewis in 2000. The fight lasted less than six minutes. The announcement received a lot of criticism and bad press from the media and fans. Two days later, Grant confirmed the fight was cancelled. On 6 August, after struggling to find an opponent, Hearn revealed that Whyte would fight 15-year veteran Malcolm Tann (24–5, 13 KOs) in a scheduled eight-round fight on the undercard of Terence Crawford vs. Julius Indongo. Whyte knocked Tann down four times en route to winning the fight via TKO in round three. Whyte admitted he needed a bigger challenge towards the end of the year before a potential world title fight.

On 11 January 2018, a fight between Whyte and Lucas Browne (25–0, 22 KOs) was finally made, to take place at The O2 Arena in London on 24 March. Whyte’s WBC Silver title would be at stake. Speaking of the fight, Whyte said, “I can’t wait, I hate Lucas Browne and I want to hurt him. He’s said some nasty things and he’s going to have to pay for them.” Whyte hit Browne with a hard left hook to the head in the round six to knock him unconscious, winning the fight. There was no count made and the fight was waved off immediately with ringside doctors attending to Browne before giving him oxygen. The fight was officially stopped at 37 seconds of the round. Browne’s face was cut and badly swollen from the clean shots landed from Whyte. Browne left himself open most of the time and tried switching stances after a few rounds. Browne suffered a cut over his left eye in round three, which got worse with each round. Whyte then bloodied Browne’s nose in round five. After the fight, Browne was stretchered from the ring and taken to a nearby hospital for precaution. In the post-fight interview, Whyte called out WBC champion Deontay Wilder for a fight in June 2018. Promoter Eddie Hearn said, “I hope the WBC make Dillian mandatory now, the fight is there for Deontay Wilder in June. We have to force the shot and after that performance, he deserves the shot.” Hearn stated there could be a possibility that the WBC order a final eliminator between Whyte and Dominic Breazeale.

Standing together, speaking to Sky Sports after the fight, Whyte gave Parker credit, “He was slick and I knew he was going to fight for the first few rounds, then come back in the final few rounds. I am annoyed I slipped at the final hurdle in the last round. I was rocked and took a few.” Whyte stated he would take another fight before the end of 2018 and ready for Anthony Joshua in April 2019, “I would like to fight Joshua again if he wants it. I’ve still got a lot to learn, so I would like to get one more in before him again.” Parker had no complaints and humble in defeat, “I gave it my best; the better man and I will come back stronger.” Parker’s trainer Kevin Barry was very vocal after the fight regarding Whyte’s rough tactics, claiming he should have had points taken off.

Following his eleventh-round knockout victory over Chisora, Whyte called out unified heavyweight champion Anthony Joshua. Joshua, who was unusually booed by many of those present at The O2 Arena, said: “If Deontay Wilder is serious and he is going to fight Tyson Fury and doesn’t want to become undisputed champion, Dillian, you will get a title shot.” On 12 January 2019, Whyte revealed that he had turned down a “severe lowball” offer from Joshua to fight him in a rematch. Whyte did not reveal the figure, however, he claimed it was lower than what he received against Chisora in December 2018. Whyte claimed the Joshua fight “was dead” and he was to look at other options, including a potential fight with Dominic Breazeale for the WBC interim title, but Breazeale challenged Deontay Wilder for the world title. WBC-NABF, IBF International, and WBO-NABO champion Óscar Rivas, had enhanced his reputation as a danger man following his brutal KO of the former world title challenger Bryant Jennings in January.

Whyte was scheduled to defend his WBC interim title against Alexander Povetkin on 2 May 2020, however, due to the COVID-19 pandemic the event was rescheduled for 22 August at the Matchroom Sport headquarters in Brentwood, Essex. Prior to the rescheduled fight, Whyte split with long-time coach Mark Tibbs. He promoted Xavier Miller from his team to head coach. Whyte lost the fight via technical knockout in the fifth round, losing his WBC interim title and mandatory position for Tyson Fury’s WBC title. Whyte started off well and controlled the fight in the first four rounds, knocking Povetkin down twice in the fourth round. However, just 30 seconds into the following round, Povetkin landed an uppercut which left Whyte flat on his back, prompting the referee to call an immediate halt to the contest.