Barcelona superstar Neymar took his tally to 50 goals in 74 games as Brazil recorded their fifth consecutive victory under new coach Tite to remain on top of South America's qualification table.
Philippe Coutinho and Paulinho also scored as the Brazilians made a triumphant return to the Estadio Mineiro, scene of their 7-1 2014 World Cup semi-final humiliation against Germany.
Brazil now head the 10-team round-robin competition with 24 points from 11 games.
But the defeat deepens the sense of crisis enveloping Argentina, who have taken just two points from their last four games and now languish in sixth place overall, one spot outside the qualifying positions for the finals in Russia.
Argentina had started brightly, with Lionel Messi drawing a foul from Fernandinho in the opening minutes which earned the Manchester City midfielder a yellow card from Chilean referee Julio Bascunan.
The Argentines created the first chance of the evening when Lucas Biglia's venomous shot from outside the area was well saved by Brazil goalkeeper Alisson on 23 minutes.
But after weathering the early pressure Brazil began to probe more effectively and on 25 minutes took the lead through Coutinho.
The Liverpool playmaker gathered the ball wide out on the left flank and accelerated purposefully towards the Argentina area.
It got better on the stroke of half-time when Neymar completed his half-century of international goals.
Another clinical Brazil attack culminated with teenage star Gabriel Jesus splitting the Argentine defence with an exquisite pass that sent Neymar through on goal.
The Barcelona striker coolly rolled his finish past the advancing Sergio Romero and Brazil were in complete control.
Neymar -- still only 24 -- is now closing in on Romario's mark of 55 goals and is firmly on track to surpass Pele's record haul of 77 goals in 91 games.
Paulinho made no mistake four minutes later though, tucking away a close range finish after a low cross from Renato Augusto.
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