Five-times winners Penarol won 3-1 at Argentine debutants Godoy Cruz while Colo Colo, the only Chilean team to have won the trophy, beat Deportivo Tachira 4-2 on coach America Gallego's debut.
Uruguay's Penarol, beaten 3-0 in their first Group Eight outing by Independiente last week, were quick off the mark as Juan Olivera chested down the ball to score after 51 seconds in Mendoza.
Godoy Cruz, who had begun impressively with a 2-1 win over former champions LDU, levelled just after the half hour with a Ruben Ramirez header.
But Olivera, who has played for clubs in South Korea, China, Saudi Arabia, Chile and Paraguay, put the visitors back in front just before half-time and Luis Aguiar added the third midway through the second half with a clever flick.
A floodlight failure halted play for 10 minutes before Penarol joined their opponents and Independiente on three points.
Ezequiel Miralles scored twice in the first half as Colo Colo, beaten 5-2 by Cerro Porteno two weeks ago, took control of their Group Five match in Venezuela.
Esteban Paredes and Lucas Vilchez doubled the scored from counter-attacks in the second half before Julio Gutierrez scored two late goals to make the score more respectable for the Venezuelans.
Tachira have one point after holding Santos to a 0-0 draw in their opening match while Colo Colo and Cerro Porteno have three each.
Gallego, a midfielder in Argentina's 1978 World Cup team, has won league titles with River Plate and Newell's Old Boys in his homeland and Toluca in Mexico.
