There was no repeat of their contentious December 2018 draw as Fury overwhelmed the previously undefeated champion before Wilder's corner threw in the towel in the seventh round on Saturday.
The Brit took a 42-pound weight advantage into a bout he described as the biggest the division had seen in 50 years and delivered on his promise to seek a knockout in Las Vegas.
Fury landed huge blows from the first bell, sending Wilder to the canvas in rounds three and five and at one point licking his opponent's blood-stained neck.
Profuse bleeding from the left ear added to the American's mounting problems as his legs became increasingly unsteady in the fifth round.
The only surprise in the end was that Wilder lasted as long as he did, having spent much of the sixth round pinned against the ropes.
— World Boxing Council (@WBCBoxing) February 23, 2020
Fury, who improved his career record to 30-0-1, commended Wilder for attempting to continue amid the pummelling.
"He came here tonight, he manned up, he really did show the heart of a champion," Fury said immediately after the fight, before leading the crowd in a rendition of the Don McLean song American Pie.
"I hit him with a clean right hand and dropped him, but he got back up and battled on into round seven.
"He is a warrior, he will be back, he will be a champion again. But I will say, the king has returned to the top of the throne!"
Wilder (42-1-1) admitted he could have no complaints, despite being disappointed with his team for throwing in the towel.
"The best man won tonight, but my side threw in the towel and I am ready to go out on my shield," he said.
"I had a lot of things going on coming into this fight, but it is what it is. I make no excuses tonight. I just wish my corner would have let me go out on my shield - I'm a warrior and that's what I do."
"But he did what he did, there are no excuses, and we will come back stronger."
Photo Getty Images Caption: Tyson Fury throws a punch at Deontay Wilder