It was the first time Ngannou had defended his title since he defeated Stipe Miocic in a knockout ten months earlier.
Gane won the interim title in the meantime by submitting Derek Lewis at UFC 265 in August of last year, becoming the first fighter in history to do so. It was Gane's 10th consecutive victory in mixed martial arts.
After years of sparring in Paris, the two former training partners finally met in California. Gane won the first two rounds before Ngannou clawed his way back into the fight.
In the third round, Ngannou landed a massive bodyslam and secured a double-leg takedown as he attempted to beat up Gane on the ground.
'The Predator' chose to wrestle once more in the fourth round, retaining his dominant position throughout the battle to tip the balance in his favour.
On the court, the final five minutes were played out on the court before Ngannou was awarded the victory by scores of 49-46 and 48-47 on two separate occasions.
When Ngannou tore his MCL during training, he considered bailing out of the fight, he said in his post-fight interview.
According to the Mirror UK, Ngannou will owe the UFC another fight as a result of his victory, but he will be free to quit the company in December if he does not fight again.
In the co-main event, Deiveson Figueiredo defeated Brandon Moreno by unanimous decision to reclaim his flyweight championship.
Moreno was aiming to defend his title for the first fight at the event, having earned the crown in a rematch against Figueiredo at UFC 263 last June in which he defeated the Brazilian.
This fight for the heavyweight championship got underway with a tense first round, with neither combatant trading combinations until the second round came to a close.
In the third round, Moreno began to look for a place to put his left hand, but he was spared by the bell when Figueiredo felled him with a right punch and attempted to tie-up a choke.
In the fourth round, there was little action, but Moreno was down once more in the fifth round, as the adversaries traded blows until the conclusion, when all three judges awarded Figueiredo the victory by a unanimous decision of 48-47.
Moreno and Figueiredo are currently tied at 1-1-1, and Figueiredo has advocated for a fourth fight between the two in his home nation of Mexico.
Michel Pereira displayed his trademark unorthodox attacks on his way to defeating UFC rookie Andre Fialho prior to the start of the co-main event.
Said Nurmagomedov, a bantamweight prospect who had not fought since October 2020, beat Cody Stamann with a guillotine choke in just 47 seconds.
Michael Morales, a welterweight from Ecuador, became only the second Ecuadorian fighter to appear in the UFC when he defeated veteran Trevin Giles in his UFC debut by first-round knockout.