It will be the Spaniard's first LaLiga start the 2019-20 following a lengthy spell on the sidelines with a cruciate ligament injury.
Asensio will start in place of Eden Hazard who was left out of the matchday squad due to fitness issues, according to head coach Zinedine Zidane.
Rodrygo Goes and Karim Benzema join the 24-year-old up front, while Eder Militao will partner Sergio Ramos at center back, with Raphael Varane unavailable after being forced off with an injury in Thursday's 1-0 win over Getafe.
Meanwhile, Gaizka Garitano has made no changes to the line-up that defeated Valencia 2-0 on Wednesday.
Raul Garcia, who scored a brace at Mestalla, will lead the line flanked by Inaki Williams, Iker Muniain and Inigo Cordoba.