The hosts took the lead early on, with Djaniny making it 1-0 in the 11th minute. Gabriel Peñalba lost the ball as he tried to play out of the back, with Djaniny driving towards goal, getting past Enzo Roco, and beating Jesús Corona to put Santos in front.
However, Cruz Azul responded quickly. In the 21st minute, Chaco Giménez switched the field for Joao Rojas, who sent a cross to the far post. Martín Cauteruccio was there to head the ball home and tie the game 1-1.
Two minutes later, Cauteruccio scored his second to put La Máquina in front. Rojas brought the ball down for the Uruguayan, who stabbed it home to make it 1-2.
Cauteruccio finished his hat-trick in the 34th minute after Omar Mendoza played him in, with the 1-3 scoreline putting the visitors firmly in control.
Santos had a few chances to reduce the deficit in the second half, but they were unable to capitalize on them. Then, in the 81st minute, their task got even harder as Jorge Sánchez earned a straight red card, leaving his team to see out the rest of the game with 10 men.
With the 1-3 win, Cruz Azul advances to the semifinals while Santos is eliminated.