The Monterrey winger replaces Roberto Alvarado , who started all three group matches for Tata Martino's men, with the Argentine manager going with what appears to be his strongest XI in the quarterfinal tie.
Pizarro is joined on the front line by Raul Jimenez and Uriel Antuna , who has been a revelation throughout the competition with his nose for goals. Antuna has netted four times through three matches despite being a late addition to the side.
Pizzaro has seen his time limited by an injury coming into the competition, but was expected to be a key character for El Tri this summer with a number of regular starters having missed out on the tournament.
They will be supported by a three-man midfield of Jonathan dos Santos, Andres Guardado and Edson Alvarez, though that trio has yet to play together from the start in the competition.
All three midfielder have seen significant time on the pitch, however, with Guardado having put in a Man of the Match performance with two goals against Canada.
Luis "Chaka" Rodríguez will resume his role at right back with Nestor Araujo and Carlos Salcedo taking up the two center-back spots for El Tri against Costa Rica's veteran attack.
Jesus Gallardo once again will be patrolling the left side of the pitch, in front of Guillermo Ochoa.
Long-time Costa Rica stars Joel Campbell and Bryan Ruiz headline the starting side for Gustavo Matosas's Ticos, where they are joined by Celso Borges and Kendall Waston.
Mexico enters the night as the favorite, having won all three of its group matches, while Costa Rica came second to upstart Haiti in its group.
The winner of the match will face the Haitians, who pulled off a stunning comeback against Canada earlier in the night, in the Gold Cup semifinals on Tuesday in Phoenix.
Mexico XI: Ochoa; Gallardo, Salcedo, Araujo, Rodríguez; Guardado, Alvarez, Dos Santos; Antuna, Jimenez, Pizarro
Costa Rica XI: Moreira; Fuller, Oviedo, Waston; Ruiz, Cruz, Leal, Borges; Campbell, George