This is the first of two meetings between the sides, who will square up once more at the Cicero Pompeu de Toledo Stadium in just over a months' time.
Sao Paulo have been in great form since they returned to league action having picked up maximum points from their last four matches.
Hernan Crespo's men defeated last year's Copa Libertadores winners Palmeiras in their last outing where they triumphed 1-0.
The Tricolor will now want to begin their continental adventure on a positive note following a disappointing campaign last time out.
However, they are no strangers to the tournament having won it three times, although their last title came all the way back in 2005.
Sporting Cristal will be hopeful of bringing their domestic form into the Copa Libertadores as they have flown out of the blocks since the Peruvian Premier Division resumed last month.
Roberto Mosquera's men have kicked their season off with four straight wins, scoring 11 goals in the process and conceding just one.
Unsurprisingly, Los Rimenses currently occupy top spot in their division with a three-point lead over their nearest challengers.
Wednesday's hosts failed to qualify for last season's edition of the Copa, and failed to make it out of the group stages when they last featured in 2019.
Their best-ever performance in the tournament came a while ago in 1997, when they fell at the final hurdle against Cruzeiro.
Mosquera is likely to stick with his regular back four considering the fact that they have let in only one goal in their last four outings.
Marcos Riquelme opened his account for the season in his side's last home fixture, and will be feeling confident ahead of the clash.
Pablo has been directly involved in five goals in his last seven games, so he is expected to be one of the key figures in deciding the outcome of this one.
Dani Alves is renowned for the numerous trophies that he has won in his career, and he will be looking to add this tournament to that long list.
Sporting Cristal possible starting lineup:
Solis; Loyola, Merlo, Castillo, Lora; Gonzales, Calcaterra, Hohberg; Avila, Riquelme
Sao Paulo possible starting lineup:
Volpi; Leo, B. Alves, Arboleda; Reinaldo, Nestor, Luan, D. Alves; Gomes, Pablo, Luciano
We say: Sporting Cristal 1-2 Sao Paulo
Both sides are in really good form coming into this one which should make for a highly entertaining clash. We are tipping the visitors to carry the day and secure all three points in this one.