After Leon took the lead at home just after the half-hour mark, Valencia equalised for Pachuca three minutes before the break and then put the visitors ahead in the 61st minute with a strong header.
Pachuca claimed a 3-1 lead with 21 minutes remaining thanks to Hirving Lozano's strike and although an own goal to Miguel Herrera reduced the visitors' advantage, Leon face a tough task to triumph in the two-legged final.
In the past four seasons, no team has lost the opening leg of a Liga MX final at home and then gone on to be crowned champions.
Dieter Villalpando was the star for Pachuca as the 22-year-old midfielder created all three goals for Enrique Meza's side.
Leon midfielder Carlos Pena produced the opening goal in the 34th minute, glancing a near-post header past Pachuca goalkeeper Oscar Perez.
Valencia dragged the visitors level eight minutes later, however, getting his outstretched boot to a free-kick from Villalpando to score at the back post.
As the match ticked into the final half-hour, Valencia and Villalpando combined again, with the former getting ahead of his marker to power the latter's corner into the net from the edge of the six-yard box.
When Villalpando released Lozano into the left-hand channel soon after, Pachuca looked to be cruising towards their first league title since the Clausura championship in 2007.
But Leon remain in contention after Herrera nodded Elias Hernandez's free-kick into his own net in the 77th minute.
Leon, who won the Apertura title in December, will travel to Pachuca's Estadio Miguel Hidalgo for the second leg on Sunday.
