The 20-year-old midfielder came off the bench against Getafe to follow in the footsteps of Marvin Park, Victor Chust, Hugo Duro and Sergio Arribas in making the jump up this term.
With the game goalless in the second half at the Coliseum Alfonso Perez, Zinedine Zidane turned to Blanco to shore up the midfield, with Toni Kroos staying on the bench.
Blanco's senior debut comes just a day after he played 90 minutes for Real Madrid Castilla in their match against Talavera de la Reina.
Coming on as a substitute against Getafe, he joined defender Chust in making his LaLiga debut at the Coliseum. The centre-back had started the match.
Sergio Arribas also came off the bench later on in the game, making it three academy players on the pitch at the same time for Los Blancos.