The City striker expertly plucked a lofted pass out of the air on the right inside four minutes before racing to the byline and cutting back for the onrushing Neymar.
The Paris Saint-Germain forward made no mistake at the far post, coolly slotting home to move within ten goals of Pele’s all-time record of 77.
Ederson was called into action soon after, expertly saving Omar Alderete’s ferocious drive from distance as Paraguay, sitting two points off automatic qualification, rallied after the early setback.
A hotly contested match in Asuncion continued to ebb and flow, and Jesus could have had a hand in another Brazil goal when he laid on for Neymar after the hour, but the forward dragged his effort wide.
City’s number 9 was substituted in the 82nd minute for Benfica’s Everton Soares after an impressive shift for the Selecao ahead of Sunday’s Copa America opener against Venezuela.
Brazil were once again thankful for Ederson's quick reflexes late on as he made a fine diving save to thwart Alberto Espinola, before Lucas Paqueta put the game to bed in stoppage time.
The substitute opened his body and curled an inch-perfect effort in off the far post to ensure Brazil maintained their 100% record and six-point cushion of second-placed Argentina after six matches.
Despite defeat, Paraguay remain sixth in the table courtesy of Chile’s 1-1 draw with Bolivia.