Striker Pablo Mouche scored in the 51st minute to give six-times champions Boca their victory over 10-man Fluminense at La Bombonera on Thursday night.
Flu, who had defender Carlinhos sent off just past the half hour for a second booking for handball, were missing injured striker Fred and midfielder Deco and failed to repeat their 2-1 win at La Bombonera in the group stage.
Boca coach Julio Cesar Falcioni made a key change at halftime bringing on striker Nicolas Blandi for midfielder Cristian Erbes, freeing Mouche to attack on the wings where he is more comfortable than in the middle.
Within six minutes of the restart, striker Dario Cvitanich passed to Mouche on the left and he scored with a low diagonal shot that beat goalkeeper Diego Cavalieri.
Flu coach Abel Braga, angry at being denied a penalty for handball by Boca defender Facundo Roncaglia in the first half, told reporters: "They had two players more, the one we had one sent off and the referee."
Velez beat holders Santos with a first-half strike from Mauro Obolo at their Fortin ground at the other end of the Argentine capital.
Obolo headed past goalkeeper Rafael at the near post from left-back Emiliano Papa's cross.
Young midfielder Gino Peruzzi kept a tight rein on Santos ace Neymar and the South American champions rarely troubled goalkeeper Marcelo Barovero.
Velez coach Ricardo Gareca, looking ahead to the second leg, said: "We had to win and not concede a goal, two fundamental things. With a team of Santos' standard nothing is certain whatever difference [in score] you take."
Wednesday's matches were draws with Universidad de Chile taking the upper hand against Libertad of Paraguay coming away from Asuncion with a 1-1 result.
In an all-Brazilian tie, Corinthians drew 0-0 at Vasco da Gama in Rio de Janeiro.
