Wilder landed a huge right hand to stop Breazeale with his 20th first-round KO and keep alive a potential undisputed unification showdown with three-belt champion Anthony Joshua.
“The power is real, it’s something that I don’t have to really train for,” said Wilder, who is convinced a showdown with Joshua will happen.
“I think it will happen. It’s going to happen. I believe in all my heart it will happen.”
Breazeale started on the front foot and tried to back up Wilder but the champion responded by landing a crunching combination.
A right hand wobbled the mandatory challenger and forced him into the corner but the Californian answered with a big right of his own to briefly send Wilder backwards.
However, the heavy-hitting knockout specialist from Tuscaloosa set up Breazeale with a short left hook before landing a huge right to send him clattering to the canvas.
Breazeale failed to make it to his feet in time to beat the count and referee Harvey Dock waved off the fight after two minutes and 17 seconds.
The victory saw Wilder extend his undefeated record to 41 wins with his 40th knockout and defend his title for the ninth time.
Breazeale suffered his second defeat in 22 fights, and first since he was stopped in seven rounds by Joshua in 2016.