Villa is Spain's all-time leading international goalscorer with 59 strikes in 97 appearances, but he has not represented his country since leaving Atletico Madrid for New York City FC in 2014.
The 35-year-old has been joined in the squad by AC Milan attacker Suso, while Saul Niguez, Marco Asensio and Gerard Deulofeu are all included after impressing during the European Under-21 Championships earlier this summer.
Chelsea's Diego Costa, however, is absent after failing to play a competitive match since the end of the 2016-17 campaign.
Spain will host Italy in their next 2018 World Cup qualifier on September 2, before travelling to Liechtenstein three days later.
Spain squad: De Gea, Reina, Kepa, Alba; Azpilicueta, Bartra, Carvajal, Monreal, Nacho, Pique, Ramos; Isco, Thiago, Busquets, Suso, Silva, Iniesta, Saul, Koke, Asensio; Aspas, Deulofeu, Vitolo, Morata, Pedro, Villa