Uruguayan side Defensor Sporting took the outright lead in Copa Libertadores Group 5 thanks to a 2-0 away victory over Real Garcilaso of Peru.
The win took Fredy Garcia's side to the 10-point mark, as they moved one clear of Universidad de Chile, who dropped down to second place after Tuesday night's game.
Juan Carlos Amado put the visitors ahead in the 50th minute with a right-footed strike following a pass by Matias Alonso.
Giorgian De Arrascaeta widened the gap four minutes later after a man-of-the-match Felipe Gedoz assist at the Estadio Huancayo.
Real Garcilaso, meanwhile, remain at the bottom of the table with just three points, having lost four of their five games.
If Cruzeiro cannot beat Universidad de Chile on Thursday, Defensor Sporting will make it into the round of 16.