Wednesday's results left all three teams on 10 points but Flamengo (+6) and LDU Quito (+4) pipped Penarol (+2) on goal difference.
River Plate progressed to the Copa Libertadores knockout stage after a win at Palestino.
Boca Juniors scored four goals against Jorge Wilstermann on Wednesday, after Cruzeiro's Fred celebrated a first-half hat-trick.
Gremio only have one point from three Group H fixtures following Thursday's 1-0 loss away to Universidad Catolica.
Playing behind closed doors at the Monumental, River Plate were held by Palestino in the Copa Libertadores.
Last season's runners-up Boca Juniors were held by Bolivian hosts Jorge Wilstermann in Group G on Tuesday.
We assess the leading candidates for glory and the potential stars ahead of the start of the 2019 Copa Libertadores.
Atletico Paranaense and Santos reached the knockout stages of the Copa Libertadores.
Flamengo top a tight Group 4 in the Copa Libertadores as Atletico Mineiro recorded a big win.