Neymar and Lucas Paqueta were on target for the Selecao, who're now six points clear at the top of the CONMEBOL group, after rivals Argentina drew earlier in the day.
The PSG star opened the scoring for the hosts just four minutes into the match by latching onto a rickety pass from Gabriel Jesus from close range, before substitute Paqueta added to the scoreline with a stoppage-time goal.
Although the Selecao were in control of the game in the opening half, it was a more even affair following the interval, but La Albirroja couldn't see the light of the day and lost for the first time in the qualifiers.
Here are the major talking points from the match:
#1 Neymar can't and won't be stopped
No matter which way you slice it, there's no denying that Neymar has been in a league of his own in the qualifiers. Entering the match, he'd scored four goals and three assists for Brazil in four games - both highest - and now incremented his figures by one in each category.
His strike today was not spectacular, but buried the chance nonetheless, something you'd always expect from him, and then created a lovely chance for Paqueta to finish with a flourish.
The PSG star is shaping up well for the Copa America and will take some stopping from opposition sides. Beware, everyone.
#2 Should Paraguay have been handed a penalty?
There was a tiny spot of controversy in the first-half when Paraguay felt they should've been awarded a penalty for a handball by Brazil's Alex Sandro, but the referee waved away the shouts and signaled the match to go on.
Replays showed Omar Alderete's header came off the defender's upper arm, which is technically not a handball, and hence was the right decision. But such incidents have led to a penalty in many other games before.