Argentine giant Boca opened its 2018 account with a 1-0 win at home to Colombian visitor Junior in Buenos Aires.
Boca was held to a scoreless draw by Alianza Lima in its Group Eight opener but it claimed maximum points midweek thanks to Cristian Pavon's 28th-minute goal.
With Carlos Tevez injured, Pavon stepped up in his absence – curling a shot beyond Sebastian Viera from the edge of the penalty area.
Gremio showed no mercy in a 4-0 rout of winless Monagas after a second-half onslaught in Porto Alegre.
After a goalless opening 45 minutes, Gremio – held by Defensor Sporting on matchday one – piled on four unanswered goals via Jael, Everton, Luan and Cicero.
Jael opened the scoring with a glancing header at the near post six minutes into the second half, before Everton double the lead 10 minutes later.
Luan sprung the offside trap as he fired low and hard past Alain Baroja with three minutes remaining, while substitute Cicero completed the comprehensive Group One win.
Penarol bounced back from its first-up defeat after accounting for Atletico Tucuman 3-1 in Group Three.
Meanwhile, Cruzeiro and Vasco played out a goalless draw in their all-Brazilian affair in Group Five.