Kell Brook suffered a nasty cut to his eye during his injury
Sheffield star Brook was playing his part in the cracking contest before he suffered a horrible swelling around his left eye that paved the way for Spence to take the stoppage.
And the classy American was not going to pass up on the opportunity as Brook took a knee in the 11th before referee Howard Foster waved it off with the defeated champion blinking in pain.
Brook did not argue, he knew it was over as he conceded defeat.
‘Special K’ admitted he could not see out of the left eye by the end and it was the right decision for the bout to be stopped even if the home crowd were left disappointed.
Brook this time had his left eye smashed up after middleweight champion Gennady Golovkin shattered his right orbital socket in his last outing.
The fans were upset to see their man lose but also to be denied seeing a 12-round finish to a pulsating fight.
Spence came to the UK with a lot of hype behind him and proved he could go on to be a great in this sport with a mature performance in his 18th outing of a so far unblemished career.
Brook has now lost twice in his 38-fight career but there was no shame here even though his dream night at Bramall Lane turned into a nightmare.
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Errol Spence Jr celebrates his title win
Bramall Lane, the famous old home of Sheffield United, played host to boxing for the first time since 1984.
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That night it was local favourite Herol Graham, one of Britain’s best to never win a world title, in action but this night was all about their current favourite.
Brook bounced on his toes to the ring built on the centre circle of the pitch where his beloved Blades play with his tune ‘All of the Lights’ sending the 27,000-strong crowd wild in a raucous atmosphere.
He used to be bounced up in the air by his uncle Johnny on the Kop stand whenever United scored.
Back then he was only six and Johnny Brook predicted then that his nephew would one day fight here.
It was the latest in a long line of predictions made by the uncle and another one was that Brook would come out of this as the winner, but unfortunately mystic Johnny would not get this one right.
Brook was up against it in his hardest fight at welterweight and coming off his first career defeat to Golovkin last September in a middleweight clash.
Spence is being built in America as the heir to Floyd Mayweather Jnr’s throne as boxing king on that side of the Atlantic and showed the potential he has here.
Kell Brook went down bravely
He had received a little less of a pleasant welcome when he walked out before Brook as the challenger with chants of “who are ya?” from the proud Yorkshire crowd.
Brook, in the candy stripe colours of his favourite football team, had been charged up on his ring walk but was patient when the first bell rang.
The pair initially stood off looking to counter or feint the other into throwing first.
When they did exchange, it was high-quality action from two highly-skilled fighters.
Spence’s southpaw jab was proving difficult to get past for Brook but, when he did in the second, he went to the body and found a way through for a right hand to the head.
It got the crowd going but only brought a smirk from Spence who retaliated with a slick combination of his own in another tight round.
Spence upped the pace at the start of the third and hurt a flustered Brook with a sharp right hook.
Brook allowed Spence to then rattle in a right hand followed up a left hook as he dropped his guard going in.
The defending champion tried to salvage the round by forcing Spence back on the ropes but he couldn’t land cleanly without being countered.
The fourth started fast with both landing their back hands before Spence sunk in a couple of body shots.
Brook responded with a right uppercut in a tit-for-tat three minutes.
Many pundits were struggling to pick a winner before this and it was proving to be the tight affair everyone expected.
Brook landed a fast right-hand counter close to the end of the fifth but there was time for Spence to retaliate with a southpaw jab and left before the bell.
The sixth round was thrilling and started with Brook catching Spence off balance which sent him into the ropes.
Spence responded with a pin-point left hand before Brook sunk a right into the American towards the end of the round.
The challenger was not wilting in his first fight in England since he lost his London 2012 quarter-final and left the country without an Olympic medal as an amateur.
Brook’s left eye appeared to start to swell in the eighth, but the man himself said afterwards he felt it go in the seventh.
Spence was lashing in the body shots too and towards the end of the ninth the American started piling on the pressure with powerful combinations.
Brook started to look in trouble before the bell and the swelling over his eye was becoming more of a concern.
The home crowd roared their man on at the start of the tenth but Brook was down after a series of heavy shots.
The referee circled as Spence smashed Brook around with superb lefts.
Somehow Brook managed to survive even with the swelling seriously hurting his vision.
Brook started the eleventh brightly but it was only brief as Spence’s shots finally forced the finish and the Sheffield man to concede defeat.
Brook was blinking as he appeared in pain and took a knee to avoid more punishment before Foster took him out of his misery by waving it off.