Herrera had hoped to clinch a second successive league title with America before taking charge of Mexico for the 2014 World Cup finals but his side lost 5-1 on aggregate following a 2-0 defeat in the first leg on Thursday.
Leon, promoted this season, clinched their sixth league title and first in 21 years with goals from striker Mauro Boselli, who had also scored in the 2-0 first leg victory, and defenders Ignacio Gonzalez and Edwin Hernandez.
Herrera was given the Mexico job full time after steering them through a playoff against New Zealand while on loan from America.
"I'm very happy, I worked extremely hard to get here," Leon defender Rafael Marquez was quoted as saying on El Universal's sports website (www.centraldeportiva.com).
"I think many took me for dead but today I can show them what I've achieved, I put all my heart into this," added the 34-year-old, who returned home from the New York Red Bulls this year to wind down his career at Leon and could now be set for a fourth World Cup.
Boselli, a Libertadores Cup winner with Argentina's Estudiantes in 2009, took his championship tally to 11 when he opened the scoring in the 12th minute.
America equalised four minutes before halftime thanks to an own goal by Gonzalez, who deflected a shot from midfielder Rubens Sambueza into the net.
The home side then played the final 35 minutes a man down after defender Francisco Rodriguez was sent off for bringing down goal-bound Matias Britos.
Gonzalez and Hernandez rubbed salt in America's wounds with two goals in the final 18 minutes and Herrera was sent to the stands for dissent.
Antonio Mohamed, who coached Tijuana to their first league title last year, will replace Herrera at America for the Clausura championship starting next month.
(Reporting by Carlos Calvo; Writing by Rex Gowar; Editing by Peter Rutherford)
