Manchester United fought back from two goals down at half time to secure a dramatic 3-2 comeback victory as Edinson Cavani's double rescued Ole Gunnar Solskjaer's side at Southampton.
Jan Bednarek's header and James Ward-Prowse's stunning free-kick sent Southampton in at the break with a two-goal lead, but United, who were forced into bringing Dean Henderson on at half-time in place of the injured David de Gea, hit back in the second half.
Cavani - also a half-time substitute, replacing Mason Greenwood at the break - set up Bruno Fernandes for United's first before the Uruguayan's 74th-minute header brought the sides level.
- Solskjaer waits on De Gea injury but praises Henderson
- Premier League table | Fixtures | Results
- How Southampton and Man Utd lined up | Match stats
There was time for even more drama as Cavani swooped in stoppage time to break Southampton hearts and rescue what looked an unlikely three points for United.
Defeat means Southampton stay fifth, while the three points take United, who move into the top half, up to seventh, five points behind league leaders Liverpool with a game in hand.
Super sub Cavani: How he turned it around for Man Utd
Ole Gunnar Solskjaer knows a thing or two about making a difference from the bench, and he'll have been delighted with the impact of super sub Edinson Cavani on Sunday. But how did the striker turn it around for Man Utd at Southampton.
How Cavani rescued Man Utd...
United were quick out of the blocks at St Mary's and they almost capitalised on some poor defending from Jannik Vestergaard which allowed Mason Greenwood to round Alex McCarthy, but the forward could only hit the side netting with his shot.
Fernandes then saw a deflected effort from distance clip the outside of the post after Marcus Rashford's penalty claims were rejected by referee Jon Moss and VAR Martin Atkinson as the hosts struggled to get a foothold in the game.
That all changed in the 23rd minute when Bednarek headed them in front against the run of play, glancing Ward-Prowse's corner past De Gea at the near post.
Southampton: McCarthy (8), Walker-Peters (7), Vestergaard (6), Bednarek (7), Bertrand (6), Romeu (6), Ward-Prowse (8), Walcott (6), Armstrong (6), Djenepo (6), Adams (6).
Subs: Long (6), Diallo (n/a), N’Lundulu (n/a).
Man Utd: De Gea (5), Wan-Bissaka (6), Lindelof (7), Maguire (6), Telles (6), Matic (6), Fred (5), Fernandes (8), Van de Beek (7), Rashford (7), Greenwood (5).
Subs: Henderson (6), Cavani (8), Williams (n/a).
Man of the match: Edinson Cavani
Saints were now suddenly on top as Kyle Walker-Peters saw a deflected shot hit the far post with De Gea beaten.
However, United were almost gifted a way back into the game when McCarthy's poor pass picked out Greenwood. McCarthy redeemed his error in fine style, blocking Greenwood's initial before diving at full stretch to block Fernandes' follow-up.
It proved to be an important moment as Southampton extended their lead soon after, Ward-Prowse whipping a fine free-kick into the top left-hand corner, with De Gea unable to claw the ball out. Ward-Prowse has now scored nine direct free-kicks since his first appearance in the Premier League in the 2012/13 season and that's more than any other player in that time, ahead of former Tottenham star Christian Eriksen and Manchester United's Juan Mata.
Henderson came on for injured De Gea at the start of the second half, while Solskjaer turned to Cavani in place of Greenwood as he looked for a response from his side.
McCarthy had to be at his best again to deny Rashford, who ignored team-mate Cavani to take on the shot.
Cavani looked to have a simple finish if picked out by Rashford, but the Uruguayan was soon into the action, firing over on the turn as United looked to build up a head of steam.
- Donny van de Beek made his first Premier League start as Mason Greenwood returned to the Manchester United line-up against Southampton. The latter and Nemanja Matic were the only changes made to the midweek Champions League win against Istanbul Basaksehir. Anthony Martial, Paul Pogba and Scott McTominay were absent from the matchday squad.
- Southampton were unchanged from Monday's draw at Wolves
The pressure would eventually see them reduce the deficit in the 60th minute, Cavani crossing for Fernandes, who took a touch before striking a low shot past McCarthy.
The pressure continued to build on Southampton and the visitors levelled with 16 minutes to play as Cavani produced a poacher's finish to head home Fernandes' deflected shot.
And with the game seemingly heading for a draw going into five minutes of stoppage time, Cavani sealed all three points, heading Rashford's cross beyond McCarthy.
What the managers said…
Southampton boss Ralph Hasenhuttl: "They played [Edinson] Cavani and he is very hard to defend against. We couldn't keep the pressure high on them. We tried everything and made a fantastic game.
"We had some fantastic moments - the best I think we can against such sides. I am very happy about what we can play today. The second half, sure, was difficult but we must see the quality and, in the end, how difficult it is to defend against the other team. I think the game was good to watch.
"He [Cavani] made the difference in the second half. He is good in the box and we know this. We had not enough relief from playing out and keeping the ball. We did it for a very long time very good. For 2-2, that is okay for us, but then we conceded a third goal. We played as good as we can today. We put everything in that is possible against such teams, but we saw a fantastic side."
Man Utd boss Ole Gunnar Solskjaer: "After the first half, we played well again. It's one of those that when you win, they don't really matter. At the end I was so proud at 2-2 because we did so well. This team is getting better and better and improving which is what I want to see. We are fit."
On De Gea's injury: "Let's have a little check on him (David de Gea). Hopefully he can be okay for Wednesday but I'm not sure. Dean (Henderson) played well though.
On Henderson: "He's a keeper who has been used to being vocal. He wants to organise the team. He had a couple of tidy saves to make. He was safe with his hands.
And finally, on Cavani: "He probably wasn't able to warm up on the pitch and then he realised he needed bigger studs. He has to be ready!
Man of the match - Edinson Cavani
Ole Gunnar Solskjaer on Cavani's performance: "Great impact of course. He is a number nine who wants to be in between the posts, he is always on the move, he wants to get in front of you and I am very pleased with him. On the training pitch, in the dressing room and during meal times, how meticulous he is... He knows what he wants to eat, how much he wants to recover - everything! It was top movement and his timing is fantastic. His hunger to get on the end of things is the key for a centre-forward. Sometimes it hurts and sometimes it doesn't but to score you have to be in there."
Sky Sports' Roy Keane: "It was always a gamble when he came to the club. People were doubting did he have the hunger and desire. We've seen proof of it today. He could prove a huge signing for Manchester United."
3 - Edinson Cavani is only the second player to be directly involved in 3+ goals in a Premier League game after coming on as a substitute for Man Utd (2 goals, 1 assist), after current manager Ole Gunnar Solskjaer scored four against Nottingham Forest in February 1999. Super.— OptaJoe (@OptaJoe) November 29, 2020
Opta stats - Away day joy continues for Man Utd
- Manchester United are the first side in Premier League history to win four consecutive away games despite trailing in each.
- United have won eight consecutive top-flight away games for the first time in their history.
- Southampton have dropped 25 points from winning positions in the Premier League since the start of last season, second only to West Ham (31).
- Man Utd have come from behind to beat Southampton for the 10th time in the Premier League, only Man Utd themselves have won as many from behind against an opponent in the competition (10 vs Newcastle).
- Bruno Fernandes is the fourth Man Utd player to score in five consecutive away games in the Premier League after Ruud van Nistelrooy (2002 & 2003), Robin van Persie (2013) and Zlatan Ibrahimovic (2017).
Live Premier League
Manchester United now host PSG in the Champions League on Wednesday evening at 8pm, before travelling to West Ham at 5.30pm, live on Sky Sports, on Saturday night in the Premier League.
Southampton travel to Brighton on Monday Night Football at 8pm on December 7, live on Sky Sports Premier League.