Playing for the first time since France's World Cup final defeat against Argentina, Tottenham goalkeeper Lloris weakly spilt Douglas Luiz's shot early in the second half and Emiliano Buendia pounced to put Villa ahead.
Lloris was left on the bench for Tottenham's draw against Brentford on December 26 as he rested after France's agonising final loss in Qatar.
The 36-year-old, who conceded three times against Argentina before France lost on penalties, might have wished he had been given longer to recover after his blunder against Villa.
Brazilian midfielder Luiz added Villa's second goal in the closing stages, leaving Antonio Conte's side to endure jeers from frustrated fans at the Tottenham Hotspur Stadium.
Tottenham had hoped the first Premier League match of 2023 would serve to kick-start their bid to qualify for next season's Champions League via a top four finish.
Instead, they suffered a New Year's Day hangover as mid-table Villa punished a lethargic display.
Fifth placed Tottenham have failed to win both of their matches since the World Cup break, a dip in form which has allowed fourth placed Manchester United to climb two points above them.
Adding insult to injury for Tottenham, it was former Arsenal boss Unai Emery who masterminded Villa's success on his return to north London.
Villa manager Emery, dismissed by Arsenal in 2019, has now won three of his four Premier League matches since replacing the sacked Steven Gerrard in November.
Son Heung-min started the match once again wearing the mask he used during the World Cup to protect his fractured eye socket.
But Tottenham's South Korean star ripped the mask off for good early in the first half, discarding it angrily after failing to control a pass.