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Brazil's Philippe Coutinho scored a stunning long range goal in the 4-0 dismantling of Paraguay
Young winger Facundo Pellistri stole the show on only his second appearance for Uruguay as the twice former World Cup winners boosted their hopes of reaching Qatar 2022 with a 4-1 win over Venezuela on Tuesday.
Chile also gave themselves a lifeline as Alexis Sanchez scored a brace in a 3-2 win at Bolivia in South American World Cup qualifying.
Ecuador inched closer to qualification with a 1-1 draw in Peru, who dropped into the inter-continental play-off spot.
Colombia's hopes all but died after failing to score for a seventh consecutive match in a 1-0 defeat in Argentina.
Goals from Rodrigo Betancur, Giorgian de Arrascaeta, Edinson Cavani and a Luis Suarez penalty saw Uruguay romp to a second successive victory under new coach Diego Alonso that propelled them into the final of four automatic qualification berths in the single South American group in which Brazil and Argentina have already booked their tickets to Qatar.
But it was Manchester United youngster Pellistri, who has spent the last year on loan at Spaniards Alaves, who shone brightest.
His mazy run set up the second goal and his trickery won the penalty converted by Suarez.
"He has what it takes to help us ... pace when one on one, the craftiness to exploit the defensive position," said Alonso.
With two qualifiers left at home to Peru and away to Chile, Uruguay's World Cup destiny remains in their own hands.
They had a dream start in Montevideo as Cavani's first minute cross was half cleared to the edge of the box where new Tottenham signing Betancur hit a sweet half volley that clipped a heel and skidded past Wuliker Farinez in the Venezuela goal.
Uruguay were dominant and doubled their lead on 23 minutes after Pellistri showed great trickery to beat three players on the right and cut the ball back for De Arrascaeta to slot home from close range.
Cavani, who had a second half goal ruled out for offside, all but sealed the victory in first half stoppage time with an opportunistic overhead kick from six yards out as Uruguay's players were lining up to finish off their weary opponents.
Pellistri continued to torment Venezuela down the right in the second half and won a penalty off Nahuel Ferraresi.
Farinez saved Suarez's spot kick but referee Bruno Arleu ordered it be retaken due to encroachment and the Atletico Madrid striker made no mistake the second time.
Josef Martinez netted a consolation on 65 minutes after a defensive mistake from Jose Gimenez.
In La Paz, veteran Sanchez scored a brilliant brace to relaunch Chile's hopes of reaching Qatar after Thursday's 2-1 defeat at home to Argentina.
The win left them three points behind Uruguay and two off Peru with two to play.
Former Barcelona and Manchester United star Sanchez, 33, rolled back the years by opening the scoring on 14 minutes with a wicked swerving free-kick before netting the killer third goal five minutes from time.
Marc Enoumba equalized for Bolivia in the first half before Marcelino Nunez gave Chile the lead again after the break. Marcelo Moreno rounded off the scoring late on but defeat leaves Bolivia all but mathematically eliminated.
"It's still not over, we've got two important games left," said Sanchez. "It was vital to win today in La Paz against tough opponents."
Third-placed Ecuador would have secured qualification with a victory in Peru as Michael Estrada gave them a second minute lead after a mistake by Alexander Callens.
But he missed the target when one-on-one with goalkeeper Pedro Gallese in the second half and Edison Flores made Ecuador pay with a far post header from Luis Advincula's cross on 69 minutes.
Colombia's miserable record-equalling seven-match goalless streak has left them with little chance of even making the inter-continental play-off.
Argentina dominated throughout in Cordoba and deserved more than Lautaro Martinez's 29th minute winner.
Brazil ended Paraguay's hopes of going to Qatar with a 4-0 thrashing in Belo Horizonte.
Philippe Coutinho scored the pick of the goals with Raphinha, Antony and Rodrygo also on target.
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