Luis Suarez returned from injury to score twice as Uruguay beat England 2-1 to breathe new life into their FIFA World Cup campaign.
Uruguay were shocked by a 3-1 loss to Costa Rica in their opening Group D fixture last Saturday, but Suarez - who was absent for that game - proved the difference in Sao Paulo on this occasion.
The fitness of the Liverpool star dominated the pre-match headlines but, as expected, he was included from the start just four weeks after undergoing minor knee surgery.
And he marked his first appearance of this World Cup with a double, nodding in a superb Edinson Cavani cross six minutes before half-time to give Uruguay the lead.
Wayne Rooney missed two glorious chances for England in the first half, first heading into the bar from one yard while scores were level before shooting straight at Uruguay goalkeeper Fernando Muslera early in the second period.
But he made amends as he tapped in Glen Johnson's smart ball across the face of goal with 15 minutes left to equalise and set up a grandstand finish.
Suarez had the final say, though, pouncing on Muslera's long ball - which flicked the head of England captain Steven Gerrard - and firing past Joe Hart with just five minutes left to all but end England's chances of reaching the last 16.
Uruguay will now head into Tuesday's clash against Italy in buoyant mood, while England, beaten in both Group D matches, need a minor miracle to qualify.
Uruguay coach Oscar Tabarez threatened to ring the changes after the Costa Rica match and he was true to his word, making five alterations, as captain Diego Lugano (knee) and defender Maxi Pereira (suspended) were not the only casualties.
In stark contrast, England were unchanged, and Roy Hodgson's faith was nearly rewarded when Rooney - the target of much criticism following their 2-1 defeat to Italy - curled a 20-yard free-kick just wide with Muslera rooted to the spot.
Phil Jagielka's mishit clearance allowed Cristian Rodriguez in at the other end, but his fiercely hit left-foot effort sailed inches over the crossbar in the 15th minute.
Diego Godin was then perhaps lucky to stay on the pitch, as the defender, given a yellow card for a handball that led to Rooney's early free-kick, caught Daniel Sturridge by the throat with his forearm, but avoided further punishment.
England should have taken the lead in the 31st minute but Rooney, who rose above Martin Caceres, inexplicably headed into the bar from one yard from a Gerrard free-kick, and they were soon made to pay for their profligacy.
Nicolas Lodeiro instigated the opener, beating Gerrard in midfield, and he fed Cavani, who, from the left, produced an inch-perfect cross that looped over Jagielka and onto Suarez's head, with the striker nodding across Hart and in from eight yards.
Sturridge nearly produced a quick response for England but they had to weather a storm after the break as Uruguay ramped up the pressure.
Suarez caught Hart napping as he shot from a corner, with the goalkeeper having to scramble back to keep it out, and he also fired wide after England were caught out at the back.
Cavani then wasted a fine chance to double Uruguay's lead, shooting wide when one-on-one with Hart before Rooney could only shoot at Muslera when played in at the other end.
Rooney finally opened his World Cup account in the 75th minute as Johnson, who cut in from the right and beat Alvaro Gonzalez, saw the Manchester United man steal in front of Caceres and shoot past Muslera.
England's celebrations were cut short, though, as Muslera's hopeful punt forward saw Suarez pounce on Gerrard's inadvertent flick-on, the striker keeping his cool to slam the winner past Hart.
|Fiorentina 2 Barcelona 1: Bernardeschi double sends Barca to another defeat|
|Mancini hints at Melo interest|
|Rodgers hails ´incredible´ Benteke strike|
|Galatasary 1 Inter 0: Sneijder sinks former club|
|Wenger defends Arsenal approach|
|Wembley loss has no bearing on new season - Terry|
|Porto cruise to friendly win over Stoke|
|Mourinho denies Wenger ´snub´ suggestions|
|Arsenal abandoned their philosophy to win Community Shield - Mourinho|
|Mourinho throws Community Shield medal into Wembley crowd|
|Swindon Town 1 Liverpool 2: Benteke nets stunner on debut|
|Scottish Premiership Review: Hearts win thriller on top-flight return|
|Ujah at the double as Bremen beat West Ham|
|Mourinho: We were the better team|
|Wenger hails defensive solidity|
|Rooney returns as Villarreal spoil Ferguson´s party|
|Rodriguez stunner earns Southampton draw as Caulker makes debut|
|Arsenal 1 Chelsea 0: Case of 14th time lucky for Wenger against Mourinho|
|Taechaubol announces Milan agreement|
|Jojic fires Cologne to latest victory|
|China 0 South Korea 2: Kim and Lee seal victory|
|Origi getting up to speed|
|Costa a doubt for start of season - Mourinho|
|North Korea 2 Japan 1: Halilhodzic´s men spurn lead|
|Allam brands FA ´amateurs´ as name-change row rumbles on|
|Fournier ´worried´ by Lyon pre-season|
|Swansea still working on Michu exit - Monk|
|Neuer furious at Bayern Supercup defeat|
|Wenger: Ozil signing not a mistake|
|UEFA Champions League Preview: Shakhtar ready for Fenerbahce decider|
|Lampard targets MLS play-offs for City|
|MLS Review: Goals galore as DC United win 10-goal thriller|
|Ronaldinho returns and helps Fluminense to win|
|Keane: United won´t overtake Chelsea|
|Casillas has the ´enthusiasm of a 20-year-old´ - Lopetegui|
|Blanc hopeful over Ibrahimovic knee injury|
|Guardiola laments late goal in Supercup defeat|
|Tuchel plans to keep Bender|
|Hecking happy with Wolfsburg discipline after Supercup win|
|Arsenal players too interested in selfies and six-packs - Keane|
|Confusion over Ibrahimovic´s PSG future|
|Sporting Lisbon 2 Roma 0: Slimani, Mane inspire Portuguese hosts|
|Rodgers feeling ready for new campaign|
|Khedira to miss Supercoppa|
|Paris Saint-Germain 2 Lyon 0: Aurier and Cavani seal more silverware|
|Wolfsburg 1 Bayern Munich 1 (5-4 on penalties): Super-sub Bendtner nicks it for Pokal champions|
|Lampard´s long-awaited New York City debut ends in defeat|
|Casillas the spot-kick hero for Porto|
|Monk bullish ahead of season opener at champions|
|Marseille 2-0 Juventus: Night to forget for Serie A champions|
|Swansea end pre-season with yet another draw|
|HJK 0 Liverpool 2: Origi and Coutinho on target|
|Juventus rocked by Khedira injury scare|
|Lens and Pantilimon star as Sunderland beat Hannover|
|Pardew hopeful of concluding Wickham deal|
|Martinez allays Lukaku fears|
|Stuttgart 4 Manchester City 2: Cause for concern for Pellegrini|
|Wasteful Bournemouth held by Hoffenheim|
|Jerome seals Norwich win|
|Souare´s first goal ensures Palace draw|
|Sinclair hits hat-trick in Villa draw|
|Leicester end pre-season with thrilling Birmingham win|
|Wood and Mowatt condemn Everton to friendly defeat|
|Coloccini not involved as Newcastle lose to Gladbach|
|Borussia Dortmund 2 Real Betis 0: Ramos scores on return from injury|
|Stoke lose to Cologne on Afellay debut|
|Norwich capture goalkeeper Kean|
|Jovetic hits out at Pellegrini following City exit|
|Jones backing new boys to spark United revival|
|Scottish Premiership Review: Celtic up and running, Dundee hammer Kilmarnock|
|Can keen to learn from Milner|
|Immobile on the mend following friendly scare|
|Sagan Tosu 1 Atletico Madrid 1 (1-4 on penalties): Simeone´s men need spot-kicks|
|Cahill: Big-spending rivals will make title race tougher|
|Roberto happy to play full-back for Barca|
|Gestede eager to make his mark at Villa|
|I want to play more and score more - Remy|
|Lambert influence important, says Pulis|
|Benteke a ´bargain´ buy - Rodgers|
|Zola: Qatar would be ideal for Balotelli, Cassano|
|Suarez: I´m not among world´s best|
|PSG ready despite ´chaotic´ pre-season - Blanc|
|Arsenal thumping still hurts - Fournier|
|Aubameyang targets Champions League success|
|Rooney set for Everton return|
|Cech can match Van der Sar - Wenger|
|Mourinho ponders Wenger´s losing record against him|
|CBF confirm Fred failed a doping test|
|Bournemouth beaten by battling Cardiff|
|Immobile injury overshadows Sevilla win at Vicarage Road|
|Lambert at the double on West Brom bow|
|Real sign up Spain starlet Vallejo|
|Valencia blow for West Ham|
|Elche cleared to play in Segunda Division|
|Baker pens a new Villa deal|
|Lambert makes Albion switch|
|Gillingham and Scally found guilty of ´race victimisation´|
|Inter complete Jovetic signing|
|Arsenal v Chelsea: Mourinho cools Wenger rivalry ahead of Wembley meeting|
|Villa snap up Gestede|
|Villa land Veretout|
|Mourinho coy on fresh Stones bid|
|Aubameyang commits to Dortmund|
|Torres on the hunt for trophies with Atletico|
|Cazorla and Walcott sign new Arsenal deals|
|Quick start vital in Arsenal title bid - Wilshere|
|I have received no offers - Guardiola|
|Barcelona to monitor Turan injury|
|Zorc ´surprised´ by Grosskreutz-Tuchel row|
|Phil Neville could be England manager - Moyes|
|UEFA to investigate Shakhtar´s Fred selection|
|City loan Unal to Genk|
|China v South Korea: Stielike looking for new options|
|North Korea v Japan: Halilhodzic to unearth new faces|
|Drogba: I want to be ready, not a burden|
|Hamstrung Clasie in doubt for Southampton league opener|
|West Ham goalscorer Zarate bemoans Astra comeback|
|Negredo quashes Valencia exit rumours|
|´This is not my Sampdoria´ - president Ferrero|
|Criscito could join Inter - agent|
|CBF endorse Zico´s FIFA presidency campaign|
|Hawit to handle CONCACAF´s referee review|
|Falcao is a ´top, top player´ - Terry|
|Tuchel pleased by Dortmund fighting qualities|
|Premier League rules out schedule changes for Champions League clubs|
|UEFA Europa League Review: Southampton stroll as Sampdoria are humiliated|