Despite finishing top of the standings after the regular season, America lost both their matches to eighth-placed Tigres during the campaign and will be on the road for the first leg.
Tigres have not lost in any of their last five games, while America has only won one of their past six matches.
Also on Saturday, Morelia hosts Leon in a battle between sixth and third position respectively.
The last meeting between the two sides entered in a 2-0 home win for Morelia with the previous encounter in Leon ending goalless.
Leon enters the finals series buoyed by a 5-0 win over Tijuana, while Morelia has won three of their past five games.
On Sunday, regular season runners-up Santos Laguna travel to seventh-placed Queretaro.
Laguna recorded a draw and loss in their last two matches leading up for finals but has previously been on a six-game winning streak that propelled them up the standings.
Queretaro have only won two of their last 10 games and lost 2-0 and drew 1-1 in their two meeting with Laguna during the campaign.
Also on Sunday, fifth-placed Toluca will take on Cruz Azul in a battle of two sides with long unbeaten streaks.
Toluca has not been beaten for 10 matches, while fourth-placed Cruz Azul are on a nine-game streak without a loss.
Cruz Azul won both games in the regular season with 2-1 and 2-0 triumphs - both in Toluca.
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