Ahead of Liverpool’s trip to Brentford later on Saturday Ole Gunnar Solskjaer’s men were looking to grab the top spot. But after an encouraging first half when they wasted a number of chances, they dropped their levels in the second half.
Villa was much the better of the two sides in the second period and they got their reward on 88 minutes through a superb header from Kortney Hause.
United though could have rescued an unlikely point but for Fernandes’ late horror miss from 12 yards.
And Solskjaer will have an anxious wait to check on the injuries to Luke Shaw and Harry Maguire, who were both substituted.
Solskjaer reverted to the team that beat West Ham in the Premier League.
The Norwegian boss made 11 changes for the Carabao Cup defeat by the Hammers in midweek. Edinson Cavani was back on the bench after a month out with a muscle strain.
United then got away with one after Harry Maguire’s poor back pass put David De Gea in trouble. He could only give it to Ollie Watkins inside the 18-yard box. But the goalkeeper managed to pull off a fantastic save at point-blank range before grabbing the ball from the Villa man.
Shaw was forced off through injury with Diogo Dalot, who spent all of last season on-loan at Milan, replacing him.
Ezri Konsa powered a header over the bar when well placed after a corner from Douglas Luiz as Villa looked for an opening. But that opening almost came at the other end in first-half stoppage time. Bruno Fernandes’ corner was flicked on by Raphael Varane and Paul Pogba threw himself at the ball at the far post with the ball bobbling past the post.
Pogba hit a curling free-kick just over the bar as United tried to get their noses in front at the start of the second half.
But there were more problems for Solskjaer when Maguire went down with what looked like a shin injury.
Victor Lindelof soon replaced him to leave Solskjaer’s attacking options from the bench limited.
Watkins almost opening the scoring on 69 minutes. He picked up the ball up on the left flank, cut inside Varane and sub Scott McTominay and hit a thunderous strike which De Gea turned away.
With the crowd calling for Cavani, Solskjaer gave the forward the nod from the bench with eight minutes to go. McTominay making way, as United looked for a late winner.
But it was Villa who though they had landed the killer blow two minutes from time.
A brilliant corner taken by Luiz found Hause at the near post, who got ahead of Cavani to direct a stooping header into the roof of the net to send Villa’s fans wild.
However, Hause went from hero to zero in a matter of seconds as the defender repelled Fernandes’ powerful cross with his hand.
The referee pointed to the spot, but Fernandes blasted his 92nd-minute penalty high over the bar.