Cruzeiro's win in Venezuela, which came after goals from Leandro Damiao and Marquinhos, was their first in three games but takes them top of Group 3 alongside Universitario of Sucre.
Both teams have five points, two ahead of Huracan and four ahead of Mineros.
Atletico Mineiro got their first points on the board on Wednesday with a 1-0 win over Independiente de Santa Fe 1-0 in Colombia. They are three points behind joint Group 1 leaders Santa Fe and Colo Colo.
Sao Paulo and Corinthians both won in Group 2, with Corinthians beating Danubio of Montevideo 2-1 and a late goal from Michel Bastos enough to help Sao Paulo overcome Libertadores holders San Lorenzo.
Internacional of Porto Alegre drew 1-1 at Emelec and are joint top of Group 4 with the Ecuadoran team.
(Reporting by Andrew Downie; Editing by Peter Rutherford)
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