A frustrated Cristiano Ronaldo was 'starved of service' as United went a second straight game without scoring and Villa claimed their first win at Old Trafford in 12 years.
The match had looked set to end goalless until Kortney Hause flicked a near-post header beyond David De Gea to give Villa a shock lead with two minutes left to play.
The drama didn't end there though as Hause almost went from hero to villain when he handled in the box in stoppage-time to concede a penalty.
Fernandes stepped up rather than compatriot Ronaldo, who had a frustrating afternoon, but fired the ball well over the bar, consigning title hopefuls United to a damaging defeat on home soil.
All game, United couldn't create chances for returning ace Ronaldo, while manager Ole Gunnar Solskjaer was also handed two huge blows with Luke Shaw and Harry Maguire both limping off injured.
Fernandes had looked to both create and score in the opening stages, firing a shot over having started a sweeping move wih a stunning pass to Shaw.
Man United have a duel-threat over free-kicks this season but an effort after five minutes, which had Fernandes and Ronaldo over, was slammed straight into the wall by the former. Anti-climax.
Mason Greenwood started the game ahead of Jadon Sancho on the right flank but, having been set free by Scott McTominay he failed to utilise a well -positioned Paul Pogba as they thrusted forward at Villa with a counter.
Ronaldo's first chance of the game came in the 11th minute but, with an itchy trigger finger, he scuffed a long range shot well wide.
Villa struggled to get into the game but their first chance should have resulted in a goal.
In-form Matty Cash surged down the right flank and his ball across the face of goal found Matt Targett at the back post but he fired agonisingly over the bar under pressure.
Such is the threat of United, the Villans were almost immediately countered but Greenwood's tame effort inside the area was gobbled up by Emi Martinez.
Fernandes wasn't too happy, though.
"It's a tame strike but Bruno Fernandes is waving his arms around. It's a simple layback to him. He can take a touch if he wants to. You can sense the frustration," said co-commentator Micky Gray.
And that was a theme too, especially when Maguire put David de Gea in all sorts of trouble with a backpass.
The Spaniard hit Ollie Watkins with his attempted clearance but saved the striker's resulting shot.
And talkSPORT's co-commentator, and ex-Premier League ace Gray reckoned the sloppiness will have annoyed both Solskjaer and De Gea.
"I think [Solskajer would] have been frustrated with how they have given the ball away, certainly in their own half. [Aaron] Wan-Bissaka on a couple of occasions, Fred, and that backpass from Harry Maguire.
"We've just seen a replay of it, if you're a goalkeeper you want a nice little ball in front of you, played into your path so you can just clear your lines. It was bouncing, it wasn't in the area he would have wanted and you could sense the frustration from the goalkeeper.
"He was saying. 'what are you doing giving me a ball like that?'"
Villa aimed to take advantage of United's predicament and they nearly did so but Ezri Konsa's back-post header from a corner flew over the crossbar.
When United turned the screw, Smith's men responded with some dutiful and dogged defending with blocks, tackles, headers, and saves denying the Red Devils.
And before the half was done both Maguire and Pogba failed to convert headers, allowing Villa to get to the break at 0-0.
In the second-half, the tables turned totally and with John McGinn pulling the strings in the middle of the park, along with smart pressing, they gave the Red Devils a torrid time.
For all the threat, though, they couldn't make the hosts pay.
United, then lost Maguire as he attempted to play on through what appeared to be a calf issue.
Having their captain playing injured appeared to hamper the Red Devils and as soon as he went off, they were back on the front-foot.
Pogba, Fernandes and Greenwood all failed with chances, but it was certainly an improvement.
Ronaldo, though, as co-commentator Gray pointed out, was completely 'starved of service'.
And their inability to feed him allowed Villa to grab the win as Hause nodded in Douglas Luiz's corner two minutes from time - but not before a huge chunk of penalty drama.