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.
Manuel Lanzini wrapped up the aggregate victory with a well-struck goal in the 71st minute, to win the leg 2-0 for the hosts in Buenos Aires.
Lanus were already virtually assured of a last-eight spot after a 4-0 first leg win over Universidad de Chile, and on their second-leg trip to Santiago, they limited the damage to a 1-0 loss.
Charles Aranguiz scored the winning goal in the leg for Universidad de Chile on 69 minutes.
In this week's first leg encounters, Coritiba blew their home leg against Itagui, slumping to a 1-0 loss.
The Brazilian hosts were trumped by a goal in the first minute after the half-time interval, as Yessi Mena fired the Colombian visitors a valuable away goal.
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.
There was better news for Brazilian club Ponte Preta, who opened up a two-goal advantage late in their 2-0 win over Colombian outfit Deportivo Pasto.
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.
Get the best features, fun and footballing frolics straight to your inbox every week.
Thank you for signing up to Four Four Two. You will receive a verification email shortly.
There was a problem. Please refresh the page and try again.