[9] On September 13, 2019, Haney defeated Zaur Abdullaev (11–0) to win the vacant WBC interim lightweight title.

[11] On the undercard of KSI vs. Logan Paul II in November 2019, Haney made his first title defense against Alfredo Santiago (12–0), and won by unanimous decision.

[14][15] Most media members predicted an easy victory for the reigning champion,[16][17][18] which was reflected in the betting odds as well, with most odds-makers having Haney as a -5000 favorite.

[22] Haney controlled the action for most of the fight, but was hurt when Linares caught him with a powerful right-left combination toward the end of the tenth round.

Haney survived the final two rounds largely by tying Linares up and negating his opponent's attempts at trying to engage with him.

After the fight, the victor announced his desire to face unified champion George Kambosos Jr. for all four major world titles in the lightweight division, stating, "Let's do it for all the belts.

"[25] In front of a sold-out crowd in Melbourne, Australia in June 2022, Haney defeated George Kambosos Jr. by outpointing and outboxing the Australian fighter to become the first undisputed lightweight champion in the four-belt era.

[27][28] Devin Haney and George Kambosos Jr. met in their rematch at Rod Laver Arena in Melbourne, Australia on October 16, 2022.

[36] However, the decision was greatly disputed, as many onlookers felt Lomachenko had done enough to win, including fellow boxers Shakur Stevenson and Jorge Linares, who had previously predicted a Haney victory.

It was described by multiple accounts as "thrilling", with Lomachenko's display against a substantially younger and larger opponent being highly lauded.

He also said he spoke with WBC president Mauricio Sulaimán and "confirmed to him directly my commitment to be a role model and my absolute rejection of discrimination of any kind.

"[47] Haney's comments were compared to Bernard Hopkins' declaration that he would "never let a white boy beat me" before his loss to Joe Calzaghe.

[47] On December 9, 2023, in an almost sold-out Chase Center in San Francisco, California, Haney moved up a weight class and challenged 35 year old Regis Prograis for the WBC super lightweight title.

Haney staggered Prograis several more times in the middle rounds, but seemed reluctant to go for the finish and instead relied on his winning formula of attacking and retreating.

[48] Haney vs Ryan Garcia was signed[49] for April 20, 2024 in Brooklyn, New York, for the WBC super lightweight title.