Liga MX side Santos Laguna moved four points clear atop Group Eight after a comfortable 3-0 victory over Venezuelan outfit Deportivo Anzoategui.
The win leaves Pedro Caixinha's men on 10 points, clear of Arsenal (six), Deportivo Anzoategui (two) and Penarol (one).
Arsenal and Penarol meet on Wednesday.
Santos Laguna opened the scoring on 13 minutes, with Andres Renteria playing a one-two with Oribe Peralta before finishing into the bottom corner from a tight angle.
Javier Orozco doubled their advantage 11 minutes into the second half at the Estadio Nuevo Corona, volleying into an open goal after a team-mate had struck the crossbar.
Carlos Quintero's clever run down the right set up the sealer in the 66th minute as he beat his marker before picking out Peralta to nod home.
Universidad Chile also moved closer to qualification after a hard-fought 1-0 victory over Peru's Real Garcilaso.
Goalkeeper Johnny Herrera scored the game's only goal from the penalty spot on 63 minutes at the Estadio Santa Laura-Universidad SEK.
Universidad Chile (nine points) have played a game more than Defensor Sporting (six) and Cruzeiro (three, plus one goal difference), while Real Garcilaso (three, minus four) look set for a group-stage exit.
Argentina's Velez Sarsfield climbed three points clear atop Group One after two goals in three minutes helped them past Bolivia's The Strongest 2-0.
Colombia's Atletico Nacional are up to second in Group Six after a 1-0 win over Nacional in Uruguay.
Group Two leaders Botafogo held on for a 1-0 win against Independiente del Valle and Santa Fe's Omar Perez scored twice in his team's 2-2 draw against Zamora, who had Juan Falcon strike a brace.
