The victory at the Azteca, with goals by midfielder Pavel Pardo and Chile's Jean Beausejour, preserved America's unbeaten record against Cruz Azul dating back to 2003.
America are the team of Paraguay forward Salvador Cabanas, who is recovering in intensive care after being shot in the head in a Mexico City bar last month.
America have nine points from five matches in the standings with Cruz Azul, runners-up to Monterrey in the Apertura final in December, on four points.
Monterrey have 10 points after their 2-1 win over Tigres UANL.
Pachuca have the second best record behind Guadalajara after Ulises Mendivil scored two goals, including a 63rd-minute equaliser, as they came from behind to win 5-3 at Puebla.
Guadalajara remain the only team with a perfect record of 15 points following Saturday's 2-0 home win over Atlante.
The "Sacred flock," the country's most popular side, scored their goals in the first five minutes, the first through striker Javier Hernandez with forward Alberto Medina lobbing Atlante's Argentine goalkeeper Federico Vilar for the second.
The Jaguars of Chiapas, under new Argentine coach Pablo Marini who replaced the sacked Luis Tena, were beaten 1-0 at home by Queretaro.
Chiapas, Atlante and Indios of Ciudad Juarez have the worst records with two points from their five games.
