The draw for the Copa Libertadores round of 16 took place in Paraguay on Monday.
The pots are set for the last 16, with the draw scheduled to take place in Paraguay on Monday.
Wednesday's results left all three teams on 10 points but Flamengo (+6) and LDU Quito (+4) pipped Penarol (+2) on goal difference.
Santiago Arzamendia scored in Tuesday's 1-1 draw away to Uruguayan hosts Nacional as Cerro Porteno topped Group E on goal difference.
Palmeiras reached the knockout phase thanks to a 4-0 rout of Melgar, while San Lorenzo also progressed despite their 1-0 loss to Junior.
River Plate progressed to the Copa Libertadores knockout stage after a win at Palestino.
Cruzeiro made it five wins from five games in Group B as Atletico Mineiro failed to progress.
After three consecutive draws, River Plate defeated lowly Peruvian side Alianza Lima 3-0 on Thursday to move up to second in the group.
Boca Juniors scored four goals against Jorge Wilstermann on Wednesday, after Cruzeiro's Fred celebrated a first-half hat-trick.
Paolo Guerrero hits a double to sink Palestino 3-2 as Brazilian side Internacional seal their place in the last 16 of the Copa Libertadores.