Colombian side Santa Fe progressed to the Copa Libertadores last 16 with a 2-1 away win over compatriots Tolima on Tuesday.
Cristian Martinez-Borja's brace saw unbeaten Santa Fe come back from a goal down to celebrate their third win in five matches.
The first half was goalless but five minutes after the interval, Yimmi Chara put Tolima ahead.
But Martinez-Borja came off the bench to score twice, the first after chasing down a lost cause and the second when he was set up by Omar Perez.
Santa Fe lead group six on 11 points, four above Tolima and Peru's Real Garcilaso, while Paraguayan giants Cerro Porteno have already been eliminated after four straight defeats.
Ecuadorian giants Emelec also advanced to the knockout stages thanks to a goalless draw away to Argentinian champions Velez Sarsfield.
Even with qualification already assured, Velez coach Ricardo Gareca fielded a strong line-up but despite an open and intense first half, the game petered out into stalemate.
Emelec boss Gustavo Quinteros told Ecuadorian radio La Deportiva 99.3: "We always try to get a positive result so I am happy with the result and the team form.
"Penarol were ahead 1-0 and suddenly we were told they were winning 3-0 so a Velez goal would put us out of the tournament. We stepped back and suffered in the final minutes. Fortunately, we achieved our aim."
Penarol cruise against Chileans
The other group four match saw Penarol take the lead in the 38th minute with a Sebastian Gallegos free-kick.
Marcelo Zalayeta doubled their lead in the 74th minute and Matias Aguirregaray consolidated the win two minutes later after Iquique keeper Rodrigo Naranjo saved a Carlos Nunez header.
Penarol coach Jorge Da Silva had mixed feelings, telling Fox Sports: "I'm calm because Penarol did what we had to but it was not in our hands.
"We won, we played better than Iquique, we scored three goals, but we are disappointed. There were some previous results that had put us in this uncertain position.
"Now we'll focus on the local league and I will feel I owe something to our fans if I don't win the Uruguayan championship."
Tigre kept alive their hopes of qualification from group two with a 3-1 win over 10-man Sporting Cristal.
Leandro Leguizamon gave the Argentinian side a half-time lead after Jesus Alvarez's error and the game was effectively put beyond doubt in a five-minute spell early in the second period.
Matias Perez Garcia made it 2-0, Alvarez was almost immediately sent off and Ruben Botta soon added the third goal. Carlos Lobaton's goal was a mere consolation for the Peruvian side.