Gremio took the lead in the 32nd minute, when Hernan Barcos and Fluminense defender Bruno combined to turn the ball over the line.
Nine minutes after the interval Andre Santos - a new signing from Arsenal - doubled the gap.
Barcos turned creator in the 79th minute when he fed Chilean forward Eduardo Vargas, who made it 3-0.
The result was in stark contrast to Gremio's 3-1 defeat against Huachipato in the opening fixture.
Barcos said: "It was a result based on how the team managed to overcome difficulties. We had to better the bad match we played last week. If we always play like tonight, teams will find it very difficult to beat us in the Libertadores."
In the same group, Venezuelan side Caracas defeated Huachipato 3-1 on the road.
Dany Cure put the visitors ahead in the 13th minute after a Claudio Munoz mistake and Louis Pena struck again for Caracas seconds before half-time.
Another defensive mistake helped Pena consolidate Caracas' lead eight minutes after the interval, while Miguel Aceval reduced the deficit with a free-kick goal at the 64th.
In Bolivia, reigning Libertadores champions Corinthians drew their Group Five opener 1-1 in San Jose.
Peru striker Paolo Guerrero opened the scoring by finishing a Fabio Santos cross early in the fifth minute of the game, before Carlos Saucedo levelled the duel on the hour.
In Buenos Aires, Velez Sarsfield thrashed Chile's Iquique 3-0.
Velez, who had lost 1-0 at Ecuador's Emelec last week, opened the scoring through Federico Insua in the 24th minute.
Ezequiel Rescaldani doubled the lead 10 minutes later with a left-foot strike and Velez made it 3-0 at the 68th, when Iquique defender Edson Puch headed a Fernando Gago free-kick into the back of his own net.
Velez boss Ricardo Gareca told reporters: "We are growing up, trying to settle down on the field. We must keep improving in all parts.
"These three points are very important to us because the group is quite even."
Uruguayan giants Penarol lead Group Four on six points after two games, followed by Velez Sarsfield and Emelec with three, while Iquique have lost both matches.