The veteran, who has 179 caps, was sent off in the loss to Argentina and was in a race to be fit for the key Group C showdown.
Edson Alvarez, the target of a failed transfer bid from Chelsea this summer, comes as a direct replacement for Guardado.
CLICK HERE TO FOLLOW SAUDI ARABIA VS MEXICO LIVE!
Raul Jimenez will have to wait for his 100th cap for his country as he is also on the bench, although Orbelin Pineda, Jorge Sanchez and Henry Martin are drafted into the first XI. People like Kevin Alvarez, Nestor Araujo and Hector Herrera are all giving up.
For Saudi Arabia, there are changes as Abdulelah Al-Malki is suspended after picking up two yellow cards. Captain Salman Al-Faraj and right-back Mohammed Al-Burayk are also absent.
Yasir Al-Shahrani is out of the tournament after his terrible facial injury in the first game of this World Cup campaign. Sultan Al-Ghanam and Ali Al-Hassan are both coming tonight.
Saudi Arabia XI: Al-Owais, Tambakti, Al-Amri, Al-Bulayhi, Al-Ghanam, Al-Hassan, Kanno, Abdulhamid, Al-Buraikan, Al-Shehri, Salem Al-Dawsari
Mexico XI: Ochoa, Sanchez, Montes, Moreno, Gallardo, Edson Alvarez, Chavez, Lozano, Pineda, Vega, Martin