Dwarfed by his enormous opponent, Usyk had to weather a storm in the middle of the fight but he came roaring back, forcing Fury to take a standing count in the ninth round as he blazed his way to victory.
The 37-year-old Ukrainian is the first boxer to hold all four major heavyweight belts at the same time and the first undisputed champ since the end of Lennox Lewis' reign in April 2000.
Usyk got the better of the opening rounds before Fury hit his stride in the fourth, engaging in some showmanship as he started to catch Usyk with vicious body shots, but the Ukrainian battled back with several stinging reminders of his power.
Usyk turned the tide in the eighth round and few would have been surprised had the referee stopped the fight in the ninth as the Ukrainian's powerful punches to the head left Fury reeling.
The previously undefeated Briton managed to hang on until the bell but he struggled through the final three rounds of the fight as Usyk chased him down to edge him out on the judges' scorecards.
"Thank you so much. ... It's a big opportunity for me, for my family, for my country. ... It's a great time, it's a great day," a tearful Usyk said in a post-fight interview in the ring, adding that he would grant Fury an immediate rematch.
In the co-main event, Australia's Jai Opetaia won a unanimous decision over Mairis Briedis of Latvia to win the vacant IBF cruiserweight title, and Ireland's Anthony Cacace scored a TKO win over Joe Cordina of Wales to retain his IBO super-featherweight title and claim the IBF belt.
