Brazil brushed aside Paraguay, condemning them to being unable to qualify for Qatar 2022, with a 4-0 triumph after goals from Raphinha, Philippe Coutinho, Antony and Rodrygo.
Argentina got past Colombia 1-0 with Lautaro Martinez netting a 29th-minute winner in Cordoba, extending their unbeaten streak to 29 games.
But with the top two already qualified, the interest in South America centres around those contending for spots, with Ecuador moving a step closer to qualification after a 1-1 draw away to Peru.
Edison Flores netted a 69th-minute equaliser for Peru after Michael Estrada had put Ecuador ahead early, denying the visitors direct passage, with a victory all that was required to clinch qualification.
Uruguay moved into fourth spot, ahead of Peru, with their second straight triumph, getting past Venezuela 4-1 in a sign they have resolved their scoring issues.
Edinson Cavani and Luis Suarez were both on the scoresheet for Uruguay, who had suffered four consecutive defeats in qualifying.
Uruguay has 22 points ahead of Peru on 21 and Chile in sixth on 19, with Colombia in seventh on 17 with two games to play.
The side that finished fifth in the standings will face a inter-confederation playoff against the fifth-ranked AFC national team, currently likely Australia or UAE.