Two-time World Cup winners Argentina -- who had taken just two points from their first three matches -- claimed their first win, downing Colombia 1-0 in Barranquilla thanks to a first half goal from Lucas Biglia.
Brazil meanwhile produced their best performance of the qualifying campaign to date with a 3-0 defeat of Peru in Salvador.
Bayern Munich star Douglas Costa scored one goal and created two others as Brazil swept aside the challenge of the Copa America semi-finalists.
In Montevideo, Uruguay gained revenge for their stormy Copa America quarter-final defeat to Chile earlier this year with a 3-0 win.
The victory pushed Uruguay up to second place in the standings with nine points from four games, three points adrift of surprise early pacesetters Ecuador, who made it four wins out of four on Tuesday with a 3-1 win over Venezuela.
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Brazil's victory over Peru left them in third place with seven points, ahead of Paraguay and Chile on goal difference.
Argentina's win in Colombia lifted them to sixth, just outside the top five qualifying spots.
But the Argentinians will feel confident that they can mount a charge back up the table when qualifiers resume in March, when injured stars Lionel Messi, Sergio Aguero and Carlos Tevez should all be fit and available once more.
The pressure on coach Gerardo Martino was eased by Biglia's 19th-minute goal, the Lazio midfielder tapping in after Cristian Zapata failed to deal with Ezequiel Lavezzi's low cross.
"We deserved to win, it is fair. We could have scored another goal," said Martino, who said his happiness was more for his players than for himself.
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Five-time champions Brazil had a virtuoso performance from Costa to thank for their win.
The Bayern star opened the scoring with a tap-in on 22 minutes from Willian's low cross and then turned provider with a jinking run and pass for Renato Augusto for Brazil's second on 57 minutes.
Brazil's third came when Costa's fierce strike was parried away by Peru keeper Diego Penny, leaving a simple finish for Filipe Luis on the rebound.
In Montevideo, all eyes were on Chile defender Gonzalo Jara and Uruguay striker Edinson Cavani as the two men lined up against each other for the first time since their infamous clash in the Copa America in June.
On that occasion Cavani was sent off after lashing out at Jara when the Chilean defender attempted to poke a finger into the Uruguayan striker's backside.
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Jara was later banned for three matches over the incident.
The lingering tension from that encounter was evident in an ill-tempered game at the Centenario and threatened to boil over around the 20-minute mark.
Amid jawing and gesturing between the teams Uruguay were awarded a free kick and captain Diego Godin slotted home the opener from the set-piece in the 23rd minute.
Things settled down in the second half. But Chile's efforts to find an equalizer were thwarted and two quick goals from Alvaro Pereira in the 61st and Martin Caceres in the 65th saw Uruguay hand Chile their first defeat of the campaign.
To compound Chile's misery, midfielder Jorge Valdivia was shown a red card after the final whistle, apparently for remarks to referee Wilmar Roldan of Colombia, who also issued seven yellow cards.
Ecuador meanwhile lead the standings after extending their 100 percent record against Venezuela in Puerto Ordaz -- Venezuela's fourth defeat in as many games.
Goals from Fidel Martinez, Jefferson Montero and Felipe Caicedo lifted Ecuador, who exploited a porous Venezuelan defence.
In the day's other game, Paraguay defeated Bolivia 2-1 in Asuncion.
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