The fight was over in less than a minute as Prescott blew Khan away
Amir Khan was knocked out inside the first minute of his WBO intercontinental lightweight title defence by Colombia's Breidis Prescott.
The Bolton boxer was put down for the first time after just 30 seconds when hit by two lefts in quick succession.
Khan, 21, managed to regain his feet but was clearly struggling.
He resumed after an eight count but Prescott unleashed another flurry and Khan hit the deck once more before being counted out after 54 seconds.
It was a first defeat for Khan, who won an Olympic silver medal at the 2004 Olympics, in the 19th fight of his professional career.
"I made a little mistake in there and couldn't get it back again. It was a stupid mistake," said Khan.
"That's boxing. One punch can change the fight. I'm fine but I need to go back to the drawing board and put it right.
"I'm a world beater and I'm going to come back stronger. I'm really sorry to my fans."
Before the fight Khan said he had been working on his much-criticised defence with new trainer Jorge Rubio, but Prescott rocked the Bolton fighter within seconds of the start.
A stiff jab snapped Khan's head back and he was soon caught by a crisp left hook.
When Khan went down for a second time the referee called the bout off
Khan managed to absorb a right hand but was then caught by a second left hook from Prescott and his legs buckled before he hit the deck.
It looked as though he would struggle to beat the count as his legs threatened to go from under him, but he managed to convince the referee he was fit to continue after taking a full eight count.
But when the bout resumed he immediately walked onto a right hand from Prescott and another right and left from the Colombian was enough to send Khan crashing and ruin his unbeaten record.
It was Khan's first fight on pay per view television and his first bout since starting to work with Cuban trainer Rubio.
Khan's promoter Frank Warren said he took responsibility for putting him in the ring with the dangerous Prescott.
"I've got to take responsibility for it," said Warren.
"This guy was recommended by the new trainer but ultimately I take responsibility and it's back to the drawing board.
"He was caught cold. We knew this guy was a dangerous puncher. He's not the first fighter to be beat and come back to win world titles. It's how you come back from it."