De Gea has not featured for the Red Devils since midway through their pre-season preparations, with manager Louis van Gaal refusing to field the goalkeeper while speculation persists over a transfer to Real Madrid.
However, the 24-year-old has been handed a spot in Vicente del Bosque's squad to face Macedonia and Slovakia, along with United team-mate Juan Mata.
Chelsea striker Diego Costa also earns a place after regaining full fitness, but Juventus forward Alvaro Morata has been overlooked.
"We are very confident in Diego Costa, that's why he is here," Del Bosque said to reporters.
"Thiago excites us, we think he'll be our future.
"[Cesar] Azpilicueta is getting continuity in the starting XI, we trust him. We can use him as central or wide player.
"Mata has been with us for almost forever. He's here for the competition in the team."
Spain host Slovakia on September 5 before facing Macedonia away three days later.
Spain squad in full:
Goalkeepers: Iker Casillas (Porto), David de Gea (Manchester United), Sergio Rico (Sevilla)
Defenders: Juanfran (Atletico Madrid), Dani Carvajal, Sergio Ramos (both Real Madrid), Gerard Pique, Marc Bartra (both Barcelona), Cesar Azpilicueta (Chelsea), Jordi Alba (Barcelon), Bernat (Bayern Munich)
Midfielders: Koke (Atletico Madrid), Sergio Busquets (Barcelona), Juan Mata (Manchester United), David Silva (Manchester City), Cesc Fabregas (Chelsea), Santi Cazorla (Arsenal), Andres Iniesta (Barcelona), Isco (Real Madrid)
Forwards: Vitolo (Sevilla), Pedro (Chelsea), Paco Alcacer (Valencia), Diego Costa (Chelsea)
