The draw for the Copa Libertadores round of 16 took 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.
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.
Nicolas De La Cruz's spectacular free-kick helped River Plate earn a draw at Internacional in the Copa Libertadores.
Lucas Viatri led Penarol to a comprehensive win over San Jose in the Copa Libertadores.
Emelec failed to open their Copa Libertadores campaign with a win as Brayan Angulo's missed penalty proved crucial against Deportivo Lara.
Cruzeiro edged Huracan in wet conditions, while Deportivo Lara's clash against Emelec had to be rescheduled due to a floodlight issue.
We assess the leading candidates for glory and the potential stars ahead of the start of the 2019 Copa Libertadores.
Gremio advanced to the knockout phase as Group 1 winners thanks to Wednesday's 1-0 victory over Uruguayan visitors Defensor Sporting.