The American, 34, sent Luis Ortiz crashing to the canvas as the crowd inside the MGM Arena in Las Vegas gasped in shock.
Wilder was actually behind on the judges' scorecards when he opened up Ortiz.
After throwing a left-handed jab, the Bronze Bomber lived up to his nickname by smashing the Cuban with a ferocious right.
Stunned Ortiz tried to get back to his feet but was counted out as Wilder extended his unbeaten record to 43 fights.
The win was the tenth time he had successfully defended his world title, tying him with Muhammad Ali.
It was yet another display of sheer power from the WBC champ who then called out Tyson Fury for the rematch – but has his eyes on a unification bout.
