Jennings (r) fought bravely but was ultimately outclassed by Cotto
Miguel Cotto stopped Britain's Michael Jennings in the fifth round at Madison Square Garden to clinch the vacant WBO welterweight title.
The Puerto Rican made a cagey start but took control of the bout in the second round with a barrage of body shots.
Jennings was knocked down twice in the fourth round, first with a body shot and then with a sweeping left hook.
The former British champion bravely fought on but the fight was stopped after he went down for a third time.
It had been a one-sided bout in front of a boisterous crowd in New York, with Jennings only ever throwing an occasional punch and Cotto seemingly able to pick him off at will.
Marks had begun to appear on Jennings' face by the start of the fourth and he caught a straight left on the nose at the start of that round which was the beginning of the end of his hopes.
Jennings, 31, was still trying to trade blows in the fifth but he was sent on to the ropes with a crunching right to the head, followed by another big left.
A straight right to the head then left a bloodied Jennings down on one knee and he looked across to his trainer Brian Hughes, who calmly motioned for him to stand up.
But referee Benji Estevez had seen enough and called the fight off.
Jennings, from Chorley, had never previously fought outside the UK or for a world title, while Cotto, 28, was in his 14th straight world title bout.
"He is a great fighter," Jennings said. "The hardest puncher I have faced.
"He was deceiving. You think you are out of his range but then he strikes. I thought I had distance from his firepower."
Cotto, the former WBA welterweight champion, lost his last fight against Mexico's Antonio Margarito last July when he was stopped in the 11th round of a thrilling contest.
If Shane Mosley wants a rematch and if the winner of Pacquaio and Hatton wants to fight, I'm always here to fight them
However, the validity of that result has been called into question since Margarito was banned for a year after it was revealed hard pads were discovered in his gloves ahead of his defeat to Shane Mosley on 24 January.
"It was great to go back into the ring and be able to study my opponent for the first couple of rounds," said Cotto after his victory.
"Then I started to go to the body and then to the head and then I started to let my hands go and I just threw my punches."
Cotto also underlined his willingness to meet either of the combatants in May's showdown between Britain's Ricky Hatton and Filipino star Manny Pacquiao.
"If Shane Mosley wants a rematch and if the winner of Pacquaio and Hatton wants to fight, I'm always here to fight them," Cotto said.
"I'm open to anything. We want to face the best fighters available and it's just a question of deciding who we're going to fight next."
Jennings offered his help to Hatton should the Manchester fighter accept Cotto's challenge.
"It would be a good fight. Different styles make for different fights and if Ricky wants some advice from me I would tell him," he said.