Hosts Monterrey - who had Hiram Mier sent off in the 35th minute - were no match for America in the first-leg clash at the Estadio Tecnologico as Mexican striker Luis Mendoza bagged a brace.
America were fortunate to book their spot in the semis, having only edged Pumas UNAM due to their superior standing in the regular-season table after the quarter-final ended 1-1 on aggregate.
But there was nothing unfortunate about America's win in Monterrey as the Mexican giants took a 33rd-minute lead via Mendoza.
Mendoza was picked out at the back post and fired the ball into the net, albeit with some help from a deflection.
It got better for America three minutes later, with Monterrey defender Efrain Velarde heading the pall past his own goalkeeper after Mier received his marching orders for a second bookable offence just seconds earlier.
The visitors completed the scoring seven minutes from time thanks to Mendoza, who side-footed the ball into an empty net to almost dash Monterrey's hopes of reaching the final.
Thursday's other semi-final saw hosts Toluca and Tigres UANL play out a goalless draw.
Both second-leg matches will be played on Sunday.
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