The 26-year-old striker was left unmarked in the box with nine minutes to go and seized on a loose ball to poke home the winner from four yards out.
River were given a bye into the quarter-finals after last 16 rivals Boca Juniors were kicked out the tournament last weekend.
River coach Marcelo Gallardo said his team had been well off the pace and could only play better in the return leg.
“We can’t play any worse than we did tonight,” Gallardo said after the game. “Cruzeiro set out their stall well and tried to get the advantage. These games are 180 minutes and we can get a goal there. We have to be smart.”
In the previous round River took a 1-0 lead from the first leg into the return against city rivals Boca but the second leg was abandoned at half time after a Boca fan attacked River players with pepper spray as they were about to take the field.
Four players were taken to hospital with inflammation of the cornea.
Boca were kicked out the competition by CONMEBOL, the South American Football Confederation, and the club were also fined $200,000 and ordered to play their next four confederation-organised games behind closed doors.
The return leg between River and Cruzeiro will take place next Wednesday with the winner facing Guarani or Argentina's Racing. The Paraguayans won the first leg 1-0 on Thursday.
Emelec beat Tigres 1-0 on Tuesday and Independiente de Santa Fe beat Internacional of Porto Alegre by the same scoreline on Wednesday.
(Reporting by Andrew Downie; Editing by Peter Rutherford)
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