Gustavo Matosas' Leon will go head-to-head with Pachuca at the Estadio Leon on Thursday, having already won the Apertura title in November.
Leon finished third during the Apertura regular season before routing America 5-1 over two legs in the decider.
Now Leon can become the first Mexican side to retain their championship since 2004, when rivals Pumas UNAM won both the Clausura and Apertura under head coach Hugo Sanchez.
And they will be full of confidence after disposing of top-two seeds Cruz Azul and Toluca en route to the Clausura final.
Leon, who finished eighth to scrape into the Clausura finals, edged Cruz Azul on away goals after the quarter-final tie finished 3-3 on aggregate, while they booked their berth in the decider with a 1-0 victory (2-0 aggregate) over Toluca on Sunday.
Carlos Pena, who was selected in Mexico's 23-man squad for the upcoming FIFA World Cup, was the hero for Leon in the second leg, putting the tie beyond doubt with his first goal in six games.
As for Pachuca, who placed sixth in the standings, they surrendered a lead in the return leg against Santos Laguna but still advanced to the final.
Leading 2-0 following the first match at home, Pachuca raced 2-1 ahead before the half-time break.
But Enrique Meza's team conceded three goals in the second half to fall 4-2 behind, though they still triumphed on away goals as the two-legged clash finished 4-4 on aggregate.
Just like Leon, Pachuca overcame higher-ranked opponents to qualify for the play-off final, having also accounted for Pumas UNAM in the quarters.
Central to Pachuca's plans will be Clausura top-scorer Enner Valencia, who has netted 12 goals this season, three more than his nearest rival Martin Bravo.
Thursday's opening leg is not the first time the two sides will have met this season, after Pachuca easily disposed of Leon 3-1 in January.
Prior to that, the pair played out three consecutive draws: 1-1 (August, 2013), 0-0 (March, 2013) and 1-1 (October, 2012).
Interestingly, Leon and Pachuca are owned by businessman Carlos Slim, who has a 30 per cent stake in each club.
