The 23-year-old joins club-mates Iker Casillas, Alvaro Arbeloa, Sergio Ramos and Isco in Vicente Del Bosque's squad for the World Cup qualifier against Finland on Friday and the friendly against Chile four days later.
According to a Madrid statement, Fernandez will take the place of Real Sociedad's Inigo Martinez, who has a thigh injury.
A Real Madrid statement read: "Nacho Fernandez has been called up for the first time by the Spain senior squad. The Real Madrid product, who will replace Inigo Martinez, enters the squad for the games against Finland and Chile.
"Fernandez has been called to the squad after being winning the European Championship with the Spanish Under-21 side in Israel this summer."