In Santiago, Sao Paulo were the better side but only registered a 1-1 draw at the San Carlos de Apoquindo stadium.
Ney Franco's team wasted a hatful chances during the first half and opened the scoring with a precise header from defender Rafael Toloi.
That the Paulistas did not score more was down to a superb performance from hosts' keeper, Cristopher Toselli, who saved his side at least three times.
In the second half, boss Juan Martin Lasarte sent Paraguayan forward Roberto Olvelar on to the pitch, as well as attacking midfielder Fernando Meneses.
And the attacking intent paid off as 20 minutes before the end, young star Nicolas Castillo levelled the match with a good move.
"We gave them the ball and suffered a lot in the first half, but we reacted after the half-time and I think we deserved the draw and maybe something more," said man-of-the-match Toselli.
The teams will clash again next Wednesday night at the Morumbi stadium to decide the first finalists.
Meanwhile in Victoria, the Northern Suburbs of Buenos Aires, Colombian side Millonarios were not unduly tested in a goalless draw against Tigre.
Hernan Torres' side controlled the ball, but they could not create any real threat to keeper Damian Albil.
Midfielder Johnny Ramirez is confident looking ahead to the second leg of the tie: "We were superior and controlled the ball. We are very strong in Bogota, I think we can make the difference at home."
The teams will meet again next Thursday.finalists.