The Londoner achieved the accomplishment by outpointing American Andre Dirrell in Boston to claim the vacant IBF super middleweight belt.
DeGale, 29 at the time, became the first UK fighter to win a professional world title and Olympic gold - the latter being at middleweight in the 2008 Olympics.
It was a gruelling 12-round contest which sparked into life in the second when DeGale was cut but recovered to knock his opponent down twice.
Despite struggling to make the count following one of those knockdowns, Dirrell responded well and controlled the bout in the middle rounds.
It took a strong showing from DeGale in the closing stages to sway the judges in his favour. One scorecard did show victory by a wide margin but the other two were close. The final scores were 117-109, 114-112 and 114-112.
"I've finally done it," DeGale said afterwards. "It's an unbelievable feeling, I'm world champ. I made history!"
DeGale went on to defend his title with victories over Lucian Bute and Rogelio Medina before a unification attempt against WBC champion Badou Jack ended in a draw.
While he didn't beat Jack, it was an instant classic which could have gone either way. It is most remembered for his tooth getting knocked out before a hilarious interview by DeGale after the fight.
He told Adam Smith: "I thought I had done enough but it was because of the knockdown. Look at my teeth - look!
"I'm still pretty but look (DeGale smiles into the camera). I lost my teeth, burst my ear, I can't hear..."
Despite congratulating DeGale, 'Chunky' was in no mood to chat to Mayweather and told him 'don't disrespect me' after he claimed Jack had done more than enough to win the fight.
After the draw to Jack, DeGale lost his IBF title to American Caleb Truax at the Copper Box Arena in 2017 but regained it in a Las Vegas rematch the following year.
He successfully defended against Fidel Munoz but then vacated the belt to face arch-rival Chris Eubank Jr in 2019.
DeGale - who never got the chance to avenge his defeat to George Groves - finished with a solid record of 25-3-1.