The 25-year-old Ecuador international held his head in shock after the injury and was carried off on a stretcher with an oxygen mask on during the Champions League clash at Old Trafford.
It came just four days after Fulham's Bobby Zamora suffered a broken leg following a routine tackle from Wolves skipper Karl Henry during their Premier League match at Craven Cottage. Zamora will be out for at least four months following surgery.
Bad break: Antonio Valencia is carried off against Rangers
Down and out: Bobby Zamora will miss at least four months after breaking his leg
Valencia's distress was played out in front of a huge live TV audience and predictably became the sole talking point from the 0-0 draw.
His was the latest in a series of high-profile, stomach-turning injuries suffered by Premier League players, injuries where a picture tells the whole story - albeit one you can barely look at. Sportsmail recalls other bad breaks suffered by Premier League footballers.
David Busst (Coventry v Manchester United, 1996)The injury against which, sadly, all others are measured.
The Coventry defender's 50th Premier League appearance proved to be his last match ever. Having collided with United duo Denis Irwin and Brian McClair, Busst suffered extensive compound fractures to both the tibia and fibula of his right leg just two minutes into the match.
Moment of impact: David Busst collides with Denis Irwin and Brian McClair
During the 12-minute treatment delay, United keeper Peter Schmeichel vomited when he saw the extend of the damage and blood had to be washed away before the game could resume.
Busst almost lost the leg and while in hospital contracted MRSA which further damaged his bone, muscle and tissue to such an extent that he was forced to quit the game.
Busst is now Director of Football in the Community for Coventry.
Alan Smith (Manchester United v Liverpool, 2006)Manchester United's 1-0 defeat to their deadly rivals in the FA Cup meant little after Smith's horrific double injury at Anfield.
Then 25, the midfielder attempted to block a free kick from John Arne Riise but broke his leg and dislocated his ankle at one and the same time.
Stricken: Wes Brown comforts the injured Alan Smith at Anfield
United boss Sir Alex Ferguson described it as 'one of the worst injuries I've seen' and even partisan Liverpool fans gave Smith a standing ovation as he was carried off semi-conscious.
Smith himself said: 'When I looked down, the leg was lying one way and my ankle was pointing towards Hong Kong so I knew I was in serious trouble.'
Expected to be out for a year, Smith returned to action within eight months. He is now at Newcastle having joined them in 2007.
Eduardo (Arsenal v Birmingham, 2008)The most emotive injury in years. The Brazil-born Croatia international felt the full force of a challenge from Birmingham's Martin Taylor at St Andrew's.
Taylor saw red while players from both sides did their best to comfort the stricken striker. Gunners team mate Gilberto Silva was the only one who could speak to Eduardo in his native Portuguese so was able to help medics as they dealt with a broken left fibula and an open dislocation of the left left ankle.
Moment of impact: Martin Taylor's high tackle on Eduardo
The injury was so bad that Sky refused to replay the incident.
Arsenal boss Arsene Wenger called for Taylor to be banned for life - although he later retracted this. Taylor insisted he had visited Eduardo in hospital and his apology had been accepted although remembered neither the visit nor the tackle.
It certainly had a bad affect on the team. Arsenal lost the lead at the top of the table and finished third.
Eduardo himself missed the next 51 weeks but scored twice on his return against Cardiff in the FA Cup. He was transferred from Arsenal to Shakhtar Donetsk in July 2010.
Luc Nilis (Aston Villa v Ipswich, 2000)Time to quit: Luc Nilis announces his retirement in 2001
Belgium striker Nilis's Aston Villa career lasted just three games and one goal.
It was ended for good after a clash with Ipswich keeper Richard Wright that left the 33-year-old with a horrifically snapped right leg at Portman Road.
The double break occurred after just four minutes but Nilis insisted: 'It was just one of those things and he (Wright) didn't do it deliberately.'
After two operations Nilis was forced to quit the game.
He is now forwards' coach at Dutch side PSV where he used to play up front with Ruud van Nistelrooy.
Djibril Cisse (Liverpool v Blackburn, 2004)A freak injury left the flamboyant France striker in agony. Chasing the ball alongside Blackburn's Jay McEveley, Cisse's studs got caught in the turf and he snapped his fibula and tibia. Cisse later revealed that had it not been for prompt attention from thetrainers at the stadium, he would probably have lost the leg below theknee.
Freak injury: Liverpool's Djibril Cisse is carried off after catching his studs in the turf
He was out for six months and after being transferred to Marseille, Cisse broke a leg playing for France and missed the 2006 World Cup.
In 2009 he signed for Panathinaikos.
Kieron Dyer (West Ham v Bristol Rovers, 2007)Injury-prone Dyer had his right leg broken in two places following a tackle from Joe Jacobson just 10 days after his West Ham debut.
Bad start: Kieron Dyer breaks his leg ten days after his West Ham debut
Dyer did not play again for 17 months and in three years with the club has still managed just 22 Premier League games.
Aaron Ramsey (Arsenal v Stoke, 2010)The Arsenal teenager, 27 games into his Gunners career and already a veteran of 11 caps for Wales, had his lower right leg broken in two places - tibia and fibula - following a tackle from Stoke defender Ryan Shawcross who was sent off in tears after seeing the extent of the injury.
This is terrible: Arsenal players react to Aaron Ramsey's injury at Stoke
Ramsey has been out since February but manager Arsene Wenger - who has borne a smouldering grudge against Shawcross ever since the incident - insists the 19-year-old will return to action in November following a nine-month layoff.
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