Mings was taken off on a stretcher in the first half after picking up the injury while challenging for the ball with Newcastle's Alexander Isak.
"Aston Villa can confirm that Tyrone Mings has sustained a significant knee injury. The defender has undergone scans and will, unfortunately, require surgery ahead of a lengthy rehabilitation process," Villa confirmed in a statement.
Villa had already lost midfielder Emiliano Buendia to a knee ligament injury on Thursday and manager Unai Emery said he was disappointed with his side's heavy loss and the injury problems.
"This week has been very tough. We lost Emi Buendia and today we lost Tyrone Mings, two important players in the squad," he told the BBC after the game.
Mings, who has been at Villa since 2019, played 35 league games for the club last season.
