Nathan Redmond and substitute Moussa Djenepo scored to seal Southampton a 2-0 win at 10-man Brighton, who had a goal ruled out through VAR for the second week running.
The 21-year-old Djenepo opened his Saints account in style when brought on after 53 minutes with an excellent right-footed curling strike two minutes later that was too much for Mat Ryan.
In the closing minutes, Redmond then poked home at the back post after Sofiane Boufal drilled across the face of goal.
Brighton had started the game the stronger until striker Florin Andone was sent off on the half hour for a dangerous high challenge on Yan Valery and they suffered a further blow when Lewis Dunk headed home (38) only for VAR to intervene after ruling Dan Burn to be offside.
Jurgen Locadia missed a sitter from five yards towards the end when he smashed a left-footed strike into the post before Redmond finished the job minutes later, earning the Saints a first league win since April.
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Brighton: Ryan (7), Duffy (6), Dunk (7), Stephens (6), Maupay (7), Andone (5), Trossard (8), March (6), Montoya (6), Propper (6), Burn (6).
Subs: Locadia (5), Gross (5), Murray (5)
Southampton: Gunn (7), Vestergaard (6), Ings (5), Adams (5), Romeu (6), Ward-Prowse (7), Redmond (8), Hojbjerg (5), Bednarek (6), Danso (5), Valery (6).
Subs: Djenepo (8), Armstrong (NA), Boufal (8).
Man of the match: Leandro Trossard
How Southampton picked off Brighton
Brighton went at a Southampton side playing Ralph Hasenhuttl's preferred 4-2-2-2 early on with Leandro Trossard and Neal Maupay causing the problems. Maupay went close in the sixth minute, but his header from Trossard's corner was narrowly deflected over.
After Brighton controlled most of the opening period, Andone had his moment of madness which changed the game. The forward went over the ball with a high challenge on Yan Valery that rightly received a red card from Kevin Friend.
Five minutes later, Brighton had the ball in the net through a Dunk header. However, VAR showed clearly Burn was offside and infringing on keeper Angus Gunn. It meant a Burn offside had ruled out a Brighton goal for the second time in two weeks having done so against Liverpool last week.
The goal in the 55th minute from Djenepo was worth waiting for as he strode forward and curled the ball beautifully with his right foot into the top corner. As Brighton continued to press for an equaliser, Redmond took advantage in the final minutes, tapping home after some neat work from Boufal.
Brighton manager Graham Potter: "I'm very proud of them and their effort and application after going down to 10 men. I thought we started the game really well and as you would expect, Southampton came into it a little bit and it was an even game, I felt.
"The red card changes the complex of the game but we got to half-time. It was on the other side of the pitch to where I was, but obviously it doesn't look good. It looks like a forward trying to protect the ball but he's gone over the top and it's not a good tackle.
"The good thing for us is that the Southampton player isn't injured because it looked like he could've been. We apologise for that because that's not what we're about.
"I thought we started the second half really well but one action leads to their goal, which can happen, but I think we could have done better. Overall, you're looking at the personality and response of the players and the effort they put in was incredible."
Southampton manager Ralph Hasenhuttl: "In the first half, with a new shape this time, we had a few good moments and chances after winning the ball to score. I think we finally had a good balance and defensively, we were well organised. It was the first time with a back four and I think it worked well.
"The important thing to us today was the clean sheet and also, it is the first time [this season] that we've taken the lead and it helps massively. You feel like you're coming on the right track and it has not been easy the last two weeks but in the Premier League, every game is hard to win and we're happy that we have the first one.
"There is no question [about the red card] and I'm very happy that Yan Valery isn't injured. It was horrible. Even then, it's not so easy to create chances. I don't think we played very well with a man more. It was not really a good game from us in the end, but after two games without a point, I think it is normal to not have much self-confidence."
Man of the match - Leandro Trossard
Brighton forward Leandro Trossard has had a flying start to his career at the Amex and though he was on the losing side today, he was a constant threat.
His interplay with Neal Maupay bodes well for the rest of the season and Southampton's defence and midfield were constantly on the backfoot when he was in possession.
Had his side kept 11 men on the pitch - and not played an hour with 10 - he could have been leading Brighton to victory rather than impressing in a home defeat.
- Southampton have won each of their last three away games against Brighton in all competitions, keeping a clean sheet each time.
- Three of the last four Premier League red cards shown by referee Kevin Friend have been to Brighton players (Shane Duffy v Crystal Palace, Anthony Knockaert v Bournemouth and Florin Andone today).
- Moussa Djenepo's goal for Southampton - his first in the Premier League - came with his first touch in the match and just 78 seconds after coming on as a second-half substitute.
Brighton travel to Bristol Rovers on Tuesday in the Carabao Cup second round (kick-off: 7.45pm) while Southampton are also in Carabao Cup action that night, visiting Fulham (kick-off: 7.45pm).