The 28-year-old Grimaldo, signed from Benfica in the close season, has been a key member of the Leverkusen side that has surged to the top of the German Bundesliga under former Spain midfielder Xabi Alonso.
Coach Luis de la Fuente has also handed a first call-up to Real Sociedad goalkeeper Alex Remiro, who replaces Kepa Arrizabalaga with the Real Madrid shotstopper injured.
Midfielder Aleix Garcia, who has starred in Girona's flying start this season in La Liga, and Atletico Madrid's Rodrigo Riquelme also appear in the squad for the first time.
However, former Manchester City defender Aymeric Laporte, now playing in Saudi Arabia for Al-Nassr, misses out with a foot injury that required stitches.
Spain have already qualified for Euro 2024 from Group A along with Scotland, having won five of their six matches.
They complete their qualifying campaign by taking on Cyprus away in Limassol next Thursday, November 16, and entertaining Georgia in Valladolid three days later.
Spain squad
Goalkeepers: Unai Simon (Athletic Bilbao), David Raya (Arsenal/ENG), Alex Remiro (Real Sociedad)
Defenders: Dani Carvajal (Real Madrid), Jesus Navas (Sevilla), Inigo Martinez (Barcelona), Pau Torres (Aston Villa/ENG), Robin Le Normand (Real Sociedad), David Garcia (Osasuna), Jose Luis Gaya (Valencia), Alejandro Grimaldo (Bayer Leverkusen/GER)
Midfielders: Rodrigo (Manchester City/ENG), Martin Zubimendi (Real Sociedad), Gavi (Barcelona), Mikel Merino (Real Sociedad), Fabian Ruiz (Paris Saint-Germain/FRA), Oihan Sancet (Athletic Bilbao), Rodrigo Riquelme (Atletico Madrid), Aleix Garcia (Girona)
Forwards: Alvaro Morata (Atletico Madrid), Joselu (Real Madrid), Ferran Torres (Barcelona), Nico Williams (Athletic Bilbao), Lamine Yamal (Barcelona), Mikel Oyarzabal (Real Sociedad)
