The 23-year-old has yet to make an appearance this season and will now face another period on the sidelines following the latest injury setback.
Real Madrid confirmed that Asencio will undergo an operation because of a stress fracture in the tibia of his right leg.
"Our player Raúl Asencio will undergo surgery tomorrow due to a stress fracture in the tibia of his right leg," the club said in a statement.
The expected recovery period is between two and four months, ruling the defender out for a significant portion of the campaign.
Asencio's absence is particularly notable because he has not yet been able to play a single minute this season.
The injury therefore delays his opportunity to establish himself within the team after entering the campaign without a competitive appearance.
The nature of the problem means Asencio must now concentrate on his recovery before returning to football.
A stress fracture in the tibia requires a period away from competitive action, with the operation followed by rehabilitation before the defender can return to training and eventually match play.
The latest setback creates another complication for the plans of Real Madrid's coaching staff.
Asencio had been available as a defensive option but has not featured this season, and his projected absence of up to four months means the club will have to manage the position without him for a substantial period.
The 23-year-old's recovery timeline will ultimately depend on his progress after surgery.
Real Madrid have confirmed the operation but have not indicated a more precise return date beyond the expected two-to-four-month period.
Asencio will therefore begin the rehabilitation process with the aim of returning to full fitness after a frustrating start to the season.
The defender's lack of appearances so far means his return will effectively represent the beginning of his campaign once he is cleared to resume competitive football.
For Real Madrid, the injury removes another defensive option at a time when squad management will be required across a long season.
The club's immediate priority will be supporting Asencio through the operation and subsequent rehabilitation while managing his absence.
The next stage will be determining how quickly the defender can progress once the surgery has been completed.
With no minutes played this season and an expected absence of between two and four months, Asencio now faces a significant wait before he can return to the pitch.