Neymar broke the deadlock in the fourth minute before substitute Paqueta completed the scoring in the third minute of stoppage time as Brazil preserved its 100 per cent record in CONMEBOL qualifying.
A 67th international goal for Neymar – only 10 adrift of all-time record holder Pele – helped send Brazil six points clear of rival Argentina atop the standings on the road to Qatar 2022.
Brazil entered the contest away to Paraguay amid continued uncertainty over the scheduled Copa America and its participation, with the Selecao squad united in its opposition of hosting the showpiece tournament on home soil.
On the field, Tite's Brazil impressed and quickly stamped its authority on the match thanks to star Neymar in Asuncion.
Neymar put Brazil ahead with a simple side-footed finish in the fourth minute after Richarlison scuppered his attempt to volley Gabriel Jesus' cross.
It was a good omen for Brazil, with the Copa America champion winning all eight of its previous games in which the Paris Saint-Germain forward had scored in World Cup qualifiers.
A ferocious long-range strike from Paraguay defender Omar Alderete almost restored parity four minutes later but Brazil goalkeeper Ederson was forced into a stunning save.
Richarlison, who almost added a second goal in the 12th minute, put the ball in the back of the net with a brilliant half-volley in the second minute of stoppage time but it was ruled out for offside.
The tempo dropped in the second half however Marquinhos went close to doubling Brazil's lead, with his header sailing just wide of the post in the 55th minute.
Richarlison was in the thick of the action with 20 minutes remaining after a dazzling run into the box however he was thwarted by Paraguay, but Paqueta struck in the 93rd minute to make sure of the points.