River Plate trailed Ecuadorian outfit LDU Loja 2-1 after their first leg in Ecuador, with their away goal meaning a 1-0 win would have got the Argentines over the line.
And when Teofilo Gutierrez struck on 36 minutes, the game was on the terms of Ramon Diaz River Plate side.
In this week's first leg encounters, Coritiba blew their home leg against Itagui, slumping to a 1-0 loss.
Fellow Brazil Serie A side Sport Recife were beaten 2-0 away to Libertad, with first-half goals to Gustavo Gomez and Pedro Benitez handing the Paraguayans a handy lead at the tie's midway point.
Fellipe Bastos struck deep into second-half injury time, to follow up Uendel's opener on 31 minutes for the hosts in Sao Paulo.
City rivals Sao Paulo were held to a 1-1 home stalemate by Chilean club Universidad Catolica, while an own goal from Bahia midfielder Diones handed a 1-0 win to Colombia's Atletico Nacional in Medellin.
