Tigres, who won the first leg 1-0, took an early lead in the second through Fernando Gorriaran, but Toluca fought back on home soil, with Helinho and Paulinho finding the net to secure a 2-1 win, and the tie remained deadlocked at 2-2 after extra time.
The visitors started the shootout poorly when Nicolas Ibanez fired over the crossbar before Toluca's Federico Pereira also missed the target.
The shootout went into sudden death, and after Tigres player Luis Manuel Garcia became the fifth player in a row to miss, Alexis Vega scored past keeper Nahuel Guzman to secure victory for Toluca.
"We faced a very prestigious opponent with a rich history. We took penalties against the league's best goalkeeper, and the guys showed tremendous composure," said coach Antonio Mohamed, who also led Toluca to victory in this year's Clausura tournament.