The Copa Libertadores quarter-finals beckon for Palmeiras after Miguel Borja's two-goal haul downed Cerro Porteno 2-0 in the opening leg of their last-16 tie.
Colombia international Borja scored a second-half brace away from home in Asuncion to put Palmeiras in a strong position on Thursday.
With former Brazil boss Luiz Felipe Scolari – who oversaw the club's only Copa Libertadores title in 1999 – back at the helm for a third spell as head coach, Palmeiras drew first blood against the Paraguayan hosts.
Borja made the breakthrough two minutes into the second half when he fired the ball past Cerro Porteno goalkeeper Antony Silva from close range.
The 25-year-old forward doubled the lead with 19 minutes remaining after unleashing a low shot beyond Silva.
Hosts Atletico Tucuman were too good for Atletico Nacional, claiming a 2-0 win in Argentina.
Leandro Diaz and Guillermo Acosta were on target to see off the Colombian visitors.
Meanwhile, 10-man River Plate held Racing Club to a goalless draw in their all-Argentinian affair.