The Ukrainian edged the bout in Riyadh, Saudi Arabia 115-112, 113-114, 114-113 on the cards following a decisive knockdown in the ninth round.
Usyk is the first undisputed heavyweight champion since Lennox Lewis, who unified three belts against Evander Holyfield in 1999.
"I feel good. A lot of people prayed for me, I love you," Usyk said afterwards.
"I'm very happy. My people will be very happy I think, it's a big win, not only for me, it's a big win for my country, for soldiers who now defend my country."
Usyk's victory, which sees him add Fury's WBC belt to his WBA, WBO and IBF collection, also hands his opponent the first defeat of his 16-year professional career.
Fury, though, believed he was on the wrong end of the decision and immediately called for a rematch in October.
"I believe I won that fight. I believe he won a few rounds but I won more of them," he said.
"Make no mistake I won that fight and I'll be back. We go back to our families and we run it back in October.
"I'm not going to sit here and cry and make excuses."
The size difference between the pair was immediate when both met in the centre and Usyk - light on his feet - negotiated some early testers from Fury.
Fury was quick to come out and play the crowd by moving his hips from side to side while in the corner with Usyk not interested in entertaining.
Usyk started round two quickly with a one-two combination which Fury laughed off before landing a solid variety of shots of his own.
The shots kept coming at pace from Fury as he fashioned a cut above Usyk's right eye and the former kept the taunting going in the corner knowing he was ahead.
A now confident Fury made a big impact in the sixth after landing a heavy uppercut and a couple of big body blows, which required Usyk to back away and reset.
The bout opened up in round eight with both fighters hitting heavily as they attempted to wrestle control off of one another.
Fury attacked first before Usyk came back, causing cuts to the nose and left side of his opponent's head.
But the momentum shifted massively in Usyk's favour in a brutal ninth round which saw Fury battered around the ring.
The referee called a knockdown after he stumbled on the ropes but was saved by the bell and somehow survived the round.
Usyk - knowing he was now in control - maintained his composure and didn't target a knockout but continued to inflict damage on Fury, who was looking ever more vulnerable.
Both men came out throwing bombs in the final round, which ended with Fury raising his hand while Usyk dropped to his knees in the centre before embracing his team ahead of the judges' scorecards.
