All three judges scored the fight 116-112 in favour of the Ukrainian, who successfully defends his WBA (Super), WBO and WBC titles.
Usyk, the only man to defeat Fury in his 16-year career, also remains unbeaten. His updated record is 23-0.
Question marks now surround Fury, who announced his retirement in 2022 before reversing that decision.
For Usyk, beating 'The Gypsy King' again has further cemented his place among boxing's greats.
"I win, it's good. Thank you, God," Usyk told BBC Sport after his triumph over Fury.
On his opponent, he added: "He is a great fighter. An unbelievable 24 rounds for my career, thank you."
There were calls for Usyk to fight Britain's Daniel Dubois - who was in attendance - in his next fight.
The Ukrainian's response? "No problem, I am ready. Next fight, no problem."