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The Mexican pound-for-pound king produced a typically spiteful eighth-round onslaught in an otherwise competitive title unification showdown, with Saunders failing to rise from his stool for the start of the ninth and his corner throwing in the towel after nasty damage inflicted upon his right eye socket by a fierce uppercut.
Victory in front of a bumper Cinco de Mayo weekend crowd of more than 73,000 people - a new record for an indoor boxing event in the USA - at the AT&T Stadium in Arlington, Texas saw Canelo add the WBO gold to his collection of WBA (Super), WBC, and The Ring super-middleweight titles.
He now has Caleb Plant’s IBF crown firmly in his sights as he looks to become the 168-pound division’s first ever undisputed champion.
While Saunders gave a solid account of himself before the eighth round after a fast start from Canelo, he was behind on all three judges’ scorecards when the fight was halted.
“He couldn’t see,” promoter Eddie Hearn said of Saunders’ injury. “I spoke to [trainer] Mark Tibbs and he said he couldn’t see and he didn’t let him go out.
“Billy boxed beautifully, but Canelo’s so strong, he took his time. Billy’s so tricky, but he busted his eye socket.
“You can see now going back there, you can see his eye. Canelo coming on strong at the back end of the fight. He’s too good.
“It was a great performance from Billy Joe Saunders, he came to win.”
On the injury that caused the stoppage, Canelo said: “I think I broke his cheek.
“The truth is I knew it.”
He added: “I guessed in the corner and told my trainer Eddie Reynoso ‘I broke his cheek’.”
“It is never easy in a moment like that,” said Tibbs of the decision to call off the bout.
“But his leading eye was damaged and I have got too much love for the man to send him out there or ask him to go out there. He couldn’t see. It was his leading eye, it is difficult. I have been injured myself in my leading eye and it is not very nice.
“He did well up until the point he got injured. He is gutted.”
In the co-main event of the night, Canelo’s compatriot Elwin Soto provided the third successful defence of his WBO junior flyweight title against Katsunari Takayama after a controversial referee’s stoppage in the ninth round.
There was also more British disappointment as Northampton’s Kieron Conway lost a split decision to France’s unbeaten 2016 Olympic bronze medalist Souleymane Cissokho, who survived a huge late scare in an otherwise impressive display as the Anthony Joshua-managed fighter was sent to the canvas in the penultimate round.
Cuban heavyweight Frank Sanchez also earned a technical decision win over Nagy Aguilera, with the fight stopped in the sixth round with the latter refusing to go on after complaining of punches to the back of the head.
There were also respective third professional victories for talented young prospects Marc Castro and Keyshawn Davis, whose brother Kelvin was victorious despite being knocked down by Jan Marsalek.
There was also a second-round stoppage for Christian Alan Gomez Duran against Xavier Wilson.