River Plate and Gremio will meet in the final four after respective wins against Independiente and Atletico Tucuman.
Gremio travelled to Argentina and drew first blood in the opening leg of their quarter-final tie thanks to Alisson and Everton.
Independiente were awarded a 3-0 victory just hours before Tuesday's return fixture after Santos fielded an ineligible player.
Miguel Borja scored a second-half brace away from home in Asuncion to put Palmeiras in a strong position on Thursday.
Corinthians booked their spot in the Copa Libertadores knockout stage as Jadson starred against Deportivo Lara.
Goals from Jaime Valdes and Esteban Paredes saw Colo-Colo edge Delfin in the Copa Libertadores.
Keno and Lucas Lima helped Palmeiras to a win over Boca Juniors in the Copa Libertadores.
Former Benfica striker Oscar Cardozo was the hero, his 90th-minute free-kick preserving Libertad's 100 per cent record in Group Three.
Boca Juniors opened their 2018 account with a 1-0 win at home to Junior in Buenos Aires on Wednesday, while Gremio and Penarol also won.
A dramatic late goal helped Cerro Porteno to a thrilling win over Defensor Sporting in the Copa Libertadores.