Mexican side Puebla surrendered the lead on two occasions as it was held to a 2-2 draw at home to Racing Club on Wednesday.
The Clausura 2015 Copa MX winners took the lead inside the opening minutes thanks to Argentine forward Matias Alustiza. The lead was shortlived, however, with Gustavo Bou restoring parity just 10 minutes later.
Alustiza put Puebla back ahead via the penalty spot, but Ricardo Noir struck 16 minutes from time to silence the home support.
Racing now holds the advantage going into the second leg thanks to its two away goals, with a spot in Group 3 up for grabs alongside Boca Juniors, Bolivar and Deportivo Cali.
Jonathan Calleri scored in his Sao Paulo debut to earn a 1-1 draw at Peruvian side Cesar Vallejo.
Vallejo took a surprise lead when Alejandro Hohberg scored inside the opening 20 minutes. The home side took its one-goal advantage into the break but Calleri equalized with a delightful chip over goalkeeper Salomon Libman in the 66th minute.
The winner of the tie will advance to Group 1 and face River Plate, The Strongest and Trujillanos.
