Leon were 5-1 winners over two legs when the two sides last met in December's end-of-season showdown, but America drew first blood in the Clausura campaign on Saturday.
Raul Jimenez was the beneficiary of referee Paul Delgadillo's decision to award a spot-kick after 67 minutes of Sunday's Liga MX clash, even though the striker looked to be outside the box when Nacho Gonzalez made his challenge
Furthermore, the tackle appeared to be a fair one, but Jimenez put that doubt to one side as he stepped up to stroke home what proved to be the winning goal from the spot.
Luis Montes was dismissed for his protests, compounding Leon's misery.
Mauro Formica's goal gave Cruz Azul a 1-0 win at Chiapas as the visitors went joint top of the table with Toluca after three games.
The striker netted after 27 minutes in Sunday's encounter to make it seven points from three matches for Luis Fernando Tena's men.
Toluca rounded off the weekend's action with a 2-0 victory over Pumas UNAM, Pablo Velazquez and Miguel Ponce with the goals.
Tigres UANL finished with nine men in a 2-0 loss at Morelia on Saturday as Juninho and Hernan Burbano saw red.
The damage had already been done, though, as Duvier Riascos and Carlos Morales scored either side of half-time to earn Morelia's first win of the season.
Veracruz managed a 1-1 home draw against Guadalajara despite Cristian Llama's dismissal, which came after Jehu Chiapas had cancelled out Israel Castro's strike for the hosts.
Santos Laguna and Puebla played out a goalless draw in Saturday's other game.
Sunday's action was not nearly as ill-disciplined but the goals flowed at Monterrey as the home side beat Queretaro 3-1.
Willian put the visitors ahead before the break, but Victor Ramos levelled matters early in the second half prior to Marlon de Jesus and Cesar Delgado sealing the points for Monterrey, who are unbeaten after three games.
Pachuca also came from a goal down to claim a home win, recovering from Hernan Pellarno's early strike for Tijuana to triumph 2-1.
Enner Valencia grabbed the equaliser and Walter Ayovi's 74th-minute penalty completed the turnaround.
Atlante recorded their first triumph of the campaign, Narciso Mina's second-half strike proving enough to see off winless Atlas.
