Leon's William Yarbrough caught Osvaldo Martinez's 37th-minute free-kick but failed to throw the ball away before falling back into the goal, which gave America a 2-0 lead.
Although Leon striker Mauro Boselli converted a penalty in the 84th minute, America held on for victory, exacting an element of revenge after they lost the Apertura final to the same opposition last season.
Leon won both the Apertura and Clausura titles in 2013-14, defeating America 5-1 over two legs in the former final.
But at home on Saturday, the defending champions started slowly, with Martinez opening the scoring for America in the 19th minute.
The Paraguayan midfielder slipped the ball through to Oribe Peralta and the Mexico international just got a toe to it ahead of an onrushing Yarbrough, squaring a pass to Martinez, who finished calmly.
Eight minutes before half-time it was 2-0, as Martinez's free-kick from 30 yards was caught by Yarbrough underneath the bar but Leon's keeper back-pedalled into the goal, only deciding to throw the ball away after he had crossed the line.
In the 81st minute, Yamilson Rivera earned a spot kick after he was fouled by Juan Carlos Valenzuela in the area.
Boselli's effort from the spot was saved but the home side were given another chance from 10 yards almost immediately, after America defender Pablo Aguilar tripped Marcos Caicedo as the Leon striker collected the rebound.
At the second attempt, Boselli made no mistake but Leon were unable to complete their comeback.
The win took America to third in the standings, behind only Monterrey and Pumas UNAM on goal difference, while Leon sit 13th.
It took just 66 seconds for the first goal of the season to be scored with Pumas hitting the back of the net in the second minute of their match at Queretaro on Friday.
Ismael Sosa volleyed into the net to give Pumas the early lead and completed his brace five minutes before half-time, while Daniel Luduena was the visitors' other goalscorer in a 3-1 win, while Puebla defeated Tijuana 1-0 on the opening day of the season.
Monterrey won by the same scoreline against promoted side Universidad Guadalajara on Saturday to claim first position in the table, while Pachuca triumphed 1-0 at Cruz Azul, Atlas were held to a scoreless draw by Tigres UANL and Santos Laguna claimed a 1-0 victory against Veracruz.
Guadalajara drew 1-1 with Chiapas on Sunday and Toluca versus Morelia finished goalless.
