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England international Mings was taken off on a stretcher during the first half of Villa's 5-1 loss at St James' Park and the club have confirmed he will now require surgery ahead of a "lengthy rehabilitation process".
The incident occurred around the 23rd-minute mark when Mings fell awkwardly in an attempt to reach the ball before Newcastle forward Alexander Isak. The 30-year-old's right leg was put in a protective boot and he received a standing ovation from both sets of supporters as he left the pitch.
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Mings is the second Villa player to suffer a serious knee injury in the past week with midfielder Emiliano Buendia having also been ruled out for an indefinite period after sustaining ligament damage during training.
Mings took to social media to signal his determination to return even better from his latest setback.
He tweeted: "I don't even know where to start but to say thank you for all of your messages of support, Villa fans.
"From the day I came here on loan, I've given everything on the pitch. I'll now give everything off the pitch to come back even better whilst supporting the team.
"To the players, fans & staff connected to @NUFC, I also want to say thank you. The applause, the messages & the medical support I received on the day was really appreciated."
Speaking of Mings' injury after the Newcastle defeat on Saturday, Villa boss Unai Emery said: "This week is very sad for us. With Emiliano Buendia, and now with Tyrone Mings.
"We have to take some days in reflection and then prepare for the game against Everton."
Villa captain John McGinn added: "Tyrone is a huge player for us. A leader.
"After losing Emi [Buendia], it is a bitter bow and we are keeping our fingers crossed for him.
"It is devastating to see him like that. Pau [Torres] comes in, we've spent a lot of money to recruit him, and we have no excuses."