With the current set of heavyweight champions largely derided, Klitschko's win will probably see him ranked as the best of the bunch as he came to life in the fifth round to win the bout two rounds later.
The giant Ukrainian started by punishing Brock with his left jab in the fifth, and while the champion suffered a cut above his eye in the sixth from an accidental head butt, he had little to worry about with a huge right knocking down the challenger face first into the canvas.
"It took me time to get my rhythm and distance," Klitschko said.
Brock was attempting to follow in the footsteps of American Shannon Briggs who took the poorly regarded World Boxing Organization title off another former Soviet in Sergei Liakhovich last week, but after failing he heaped praise on the victor.
"He had a better jab than I thought," Brock admitted. "I saw the punch coming, but couldn't get out of the way. He's the best fighter I have ever fought."
Vladimir Klitschko: Number One
The fight was Klitschko's first defence of the title and the victory improved his overall record to 47-3, while Brock fell to 29-1.
After the bout, Klitschko reiterated his desire to unify the title.
"I will fight anybody with a belt," he said of his preferred next opponent.
Apart from Briggs, Nicolay Valuev holds the World Boxing Association crown while Oleg Maskaev owns the World Boxing Council version of the title.
The undefeated Laila Ali improved her record on the undercard with her 20 win inside the distance.
The daughter of former heavyweight champ Muhammad Ali made her Madison Square Garden debut and took just four rounds to defeat Shelley Burton to improve her overall record to 23-0.
He legendary father watched from ringside.
"I'm on a high fighting here," she said. "It feels great to be fighting in front of my father."