The decisive fifth-round stoppage made Gaethje the interim lightweight champion.
Gaethje pummeled Ferguson throughout the fight, landing 100 significant strikes to his head and 143 overall.
It wasn't the only major blow to Ferguson, however. It is now Gaethje who will likely get a shot at Khabib Nurmagomedov next, not Ferguson, who has seen five fights scheduled against The Eagle and subsequently canceled.
Few fighters have had more success than Ferguson with less hardware to show for it:
Even Nurmagomedov put aside his past rivalry with Ferguson to wish him well Sunday:
Ferguson's future is now unknown, with his orbital fracture likely sidelining him for quite some time. Gaethje, meanwhile, will likely defend his title against Nurmagomedov in a future fight that should be a fascinating contrast of styles between his brawling stand-up game and Nurmagomedov's legendary ground-and-pound.
And Gaethje isn't particularly interested in his interim belt.
"I'm waiting for the real one," he said after his win, per Brian Campbell of CBS Sports. "I knew I was a killer stepping in here. I'm good bro. No better drug on earth than adrenaline coursing through my veins.
"I have a world-class coach," he added. "I had to lose to change. You can't fix what's broken. Once I understood what was wrong, I was getting hit too much and I was having too much fun. Both times I lost, I was having too much fun. At this level, you cannot do that."