Brazil have thus become the first team, not including the hosts Russian Federation, to qualify for the World Cup.
Real Madrid full-back Marcelo made it 3-0 via a fine chipped effort to seal an impressive win for Brazil which sees them qualify for Russian Federation after going nine points clear of second-placed Colombia.
Liverpool forward Philippe Coutinho, FC Barcelona striker Neymar and Real Madrid's Marcelo scored Brazil's goals.
Neymar also missed a penalty as his side moved nine points clear of second-placed Colombia.
Neymar was on target as Brazil routed Uruguay 4-1 in last week's top-of-the-table clash to open a seven-point advantage and the 25-year-old revealed his Barcelona team-mate is impressed.
Argentina is holding onto the fifth spot, wavering at the loss of forward Lionel Messi, who became hot tempered to an assistant referee and cost him four global matches. The Brazil and Paraguay have met each other lastly in the World Cup Qualifying - CONMEBOL, the game drawn by the final score of 2-2 on 30th March 2016. According to the players, that triumph gave Brazil some confidence back.
Brazil's Renato Augusto celebrates his side's first goal against Paraguay during a 2018 World Cup qualifying soccer match at the Arena Corinthians Stadium in Sao Paulo, Brazil, Tuesday, March 28, 2017.
And their place in next year's finals was secured after Uruguay were downed 2-1 by Peru.
Brazil no longer depend exclusively on Neymar, and can play without teenage target man Gabriel Jesus and still score goals.
Messi was initially named in head coach Edgardo Bauza's line-up on Monday, but a suspension imposed by Federation Internationale de Football Association on the day of the game - after the captain insulted a match official in last week's victory over Chile - ruled him out of contention. "I will have a caipirinha [cocktail] this big", Tite said, spreading his hands. And I've always said that Brazil have a lot of high quality players. I am very happy for this moment, not only for me, but also my team-mates.
"Everything changed", winger Marcelo said. Second-place Colombia has 24 points total from its 14 games.