The battle between the Mexican top-flight's two most successful clubs was one-sided as America crushed Guadalajara 4-0 in the 'El Clasico de Clasicos'.
Luis Gabriel Rey netted a brace in the opening 15 minutes at the Estadio Omnilife before Raul Jimenez and Luis Mendoza scored after the break.
The win lifted America to fourth in the Liga MX table, nine points adrift of stuttering league leaders Cruz Azul.
Cruz Azul suffered a 3-1 loss at home to Atlas on Saturday, failing to collect maximum points in the league for the third time in their past four outings.
But Sunday's derby was the highlight of matchday 13 and America needed just 15 minutes to take control.
It was a simple opener on nine minutes as Rey was picked out at the back post and tapped in the easiest of goals.
Just six minutes later and Rey was at it again but with more style, as the forward picked up a loose ball and struck with a stunning 30-yard effort.
Jimenez scrambled in a third on 56 minutes before Mendoza completed the scoring with a lob soon after.
Cruz Azul's advantage at the top has been cut to just a point after yet another loss, the latest at home to Atlas.
Marco Fabian had cancelled out Martin Barragan's third-minute opener and the hosts looked the more likely to go ahead.
But Maikon Leite and Barragan both scored before half-time for eighth-placed Atlas and they held on.
Toluca closed in on Cruz Azul after Raul Nava's 90th-minute winner saw them past Tigres UANL 2-1.
Oribe Peralta's brace helped Santos Laguna to a 2-1 win over Pumas UNAM while Veracruz overcame Pachuca 3-1.
Ricardo Jesus netted twice in Queretaro's 2-1 win over Tijuana, Monterrey held on for a 3-2 win over Atlante and Chiapas edged Morelia 1-0.
Puebla and Leon played out a 1-1 draw.
