River Plate's quest to repeat as Copa Libertadores champions was thwarted by Ecuadorian club Independiente del Valle in the round of 16.
The Argentine club lost to Independiente by a final aggregate score of 2-1, after failing to overcome a two-goal deficit from the first leg in Ecuador.
River dominated possession and shots on goal, but could only find the net once, when substitute Lucas Alario scored from close range to give the hosts a late 1-0 lead in the 79th minute.
A four-goal lead from the first leg helped Sao Paulo hold off a valiant showing by Liga MX club Toluca, who won 3-1 at home but lost 5-3 on aggregate to the Brazilian team.
The home side struck early though a Fernando Uribe header in the 18th minute to get the comeback effort started on the right foot. However, Sao Paulo leveled in the 51st minute, making Enrique Treverio's 61st minute goal and Uribe's second as time was running out irrelevant.
Sao Paulo, who finished the match with 10 men after Ricardo Centurion was sent off, did just enough work on the day to keep their hosts at bay and move on to the quarterfinals.
The loss by Toluca means that Pumas, who beat Deportivo Tachira 2-1 on aggregate, are the sole remaining Liga MX club in the tournament.