Last year's Apertura champions, Leon are on track for an unlikely title after finishing eighth in the regular season to sneak into the play-offs.
After eliminating top side Cruz Azul, they edged Toluca 1-0 at home on Thursday.
Luis Montes scored the only goal of the game midway through the first half at the Estadio Leon, giving Gustavo Matosas' men the advantage ahead of the second leg on Sunday.
Montes headed in from the centre of the area after a well-weighted cross from the left.
In the other semi-final tie, Pachuca are in an even better position after overcoming Santos Laguna 2-0 at their Estadio Miguel Hidalgo home.
Diego de Buen opened the scoring with a 30-yard free-kick a minute before half-time, with his strike taking a deflection before beating Oswaldo Sanchez.
The sealer in the 64th minute was scrappy.
A corner was floated into the area and went uncleared before Hugo Rodriguez scrambled in from close range to complete the win.
