The West Midlands outfit had made the trip to Belgium looking to become the first team to ever win their opening four games in history in the Champions League.
However, Villa succumbed to a 1-0 defeat after a second-half penalty from Hans Vanaken condemned the Premier League side to defeat at the Jan Breydel Stadium.
Brugge earned their spot kick courtesy of Mings picking the ball up to roll back to goalkeeper Emiliano Martinez, seemingly unaware that play had restarted through Martinez's short pass to him.
Mings - making his first-ever start in the Champions League League - looked on in bewilderment, yet the assistant and VAR supported the referee in making his final decision.
What has Emery had to say?
In the aftermath of the incident, Emery cut a frustrated figure, seemingly defending Mings when venting his anger towards the officials.
Nevertheless, it was a different story when speaking at a press conference after the match, the Spaniard laying blame at the feet of Mings.
The Spaniard said, as quoted by Birmingham Live: "It is very strange this mistake, but it is football. It's the biggest mistake [his team has made] in my career as coach.
"We can make a mistake in the build up, but we work to try and control the games through possession. We did the first half fantastic.
"We lost one or two balls, but this mistake is very, very strange. It's not for Tyrone Mings or Emi Martinez. It's only happened one time in all my life. Today."
He added: "We have to forget quickly. This mistake is not going to repeat again, I think never in my life."
Where does the defeat leave Villa?
Villa will still reach the halfway stage of their Champions League campaign sitting in the top 10 of the standings.
That said, they will now play host to Juventus on matchday five under pressure to avoid defeat as they bid to remain in contention for a place in the first eight.
Emery's biggest concern will be witnessing his side go four matches without a win in all competitions, failing to defeat Bournemouth, Crystal Palace or Tottenham Hotspur prior to Wednesday's game.
A trip to Liverpool lies ahead on Saturday evening ahead of the international break.