The 35-year-old quit international football after the 2014 World Cup, having scored 59 goals in 97 appearances for La Roja. However, Lopetegui has named him in his 26-man panel for Spain's upcoming World Cup qualifiers with Italy and Liechtenstein.
Since moving to Major League Soccer in 2015, the striker has scored 60 goals in 87 league appearances for NYCFC, being named the MLS MVP in 2016. Villa replaces Diego Costa in the squad, with the Chelsea frontman yet to play this season due to an ongoing transfer dispute with Blues boss Antonio Conte regarding a move to Atletico Madrid.
Lopetegui is happy to have Villa back in the squad, telling reporters that he can be a good addition up front for the upcoming qualifiers.
"We believe he can help us," the former Porto boss said. "He gives us mobility and is especially eager. We hope and trust he will help us."
Chelsea's Marcos Alonso is a notable absentee from the squad, despite an impressive start to the Premier League season. Lopetegui revealed that he is watching him, but does not consider him an option in the current squad, and may reappraise him in the future.
"We saw Marcos Alonso live and he was fine," he continued. "We have followed him and do not rule out his presence in the future."
GK: De Gea, Reina, Kepa
DF: Jordi Alba, Azpilicueta, Bartra, Carvajal, Nacho, Monreal, Pique, Ramos
MD: Isco, Thiago, Busquets, Suso, Silva, Iniesta, Saul Niguez, Koke, Asensio
FW: Aspas, Deulofeu, Vitolo, Morata, Pedro, Villa