Match ends, Sheffield United 0, Southampton 2.
Southampton won for the first time in 10 Premier League matches as Che Adams' spectacular strike helped Ralph Hasenhuttl's side claim all three points at Sheffield United, whose slim survival hopes took another blow at Bramall Lane.
Adams rifled a half-volley into the top corner four minutes into the second half, ending a run of 16 games without a goal in all competitions.
Saints, who lost Danny Ings to an early injury, had broken the deadlock when James Ward-Prowse sent Aaron Ramsdale the wrong way from the penalty spot following Ethan Ampadu's clumsy challenge on Nathan Tella.
Takumi Minamino should have added a third for Southampton when he fired wide from Ryan Bertrand's low cross, while Adams, Nathan Redmond and Stuart Armstrong all went close late on.
"The first win after such a long time is always the most difficult one, now we have to keep on improving," Hasenhuttl told BBC Sport afterwards.
"We are looking in every direction and we still had some moments today in the game where we were not that controlled. But it's normal after such a long run without a win."
On Ings' injury, Hasenhuttl added: "I do not know yet [how serious it is]. It doesn't look that good and it is a muscle injury."
The Blades had opportunities of their own but only tested Fraser Forster twice throughout the 90 minutes.
The win lifts Saints 10 points clear of the relegation zone, while Chris Wilder's side remain rooted to the foot of the table - 12 points from safety.
Saints back to winning ways as Hasenhuttl reaches 100 not out
Southampton fans could have been forgiven for casting nervous glances towards the bottom three following their 1-0 defeat at Everton on Monday, but this win - their first in the league since beating Liverpool on 4 January - will go some way towards easing their relegation fears.
The visitors were able to call upon Kyle Walker-Peters, Ibrahima Diallo and Minamino following injury but were dealt a blow when Ings was forced off with what appeared to be a groin problem inside the opening 15 minutes.
Saints, driven on by the impressive Tella, soon recovered from that early setback and took a deserved lead when Ward-Prowse sent Ramsdale the wrong way from 12 yards after Ampadu's lunge on the Southampton youngster.
Ward-Prowse has now been directly involved in 26 Premier League goals under Hasenhuttl, twice as many as under any other Saints manager.
Adams, who last made the scoresheet against Sheffield United back in December, ended his goal drought in spectacular fashion early in the second half, thumping Armstrong's knock-down into the top corner.
Hasenhuttl's side could have won by a more handsome margin, but Minamino spurned a glorious chance to register his third goal in five league appearances for the club when he somehow failed to hit the target from Bertrand's cut-back.
Ramsdale did well to stop Tella's low strike from nestling in the far corner before thwarting Adams and Redmond from similar positions inside the area, but Hasenhuttl will gladly settle for a 2-0 victory on his 100th game in charge of the club.
Time running out for beleaguered Blades
Blades manager Wilder had called on his players to reproduce the "desire, spirit and commitment" they showed in their 1-0 win over Aston Villa, in which they survived more than 30 minutes with 10 men.
While there was no questioning United's character against Saints, the closest Wilder's side came to getting on the scoresheet in the first half was when David McGoldrick shot tamely into Forster's arms after Diallo had given the ball away in midfield.
Kean Bryan directed a close-range header over the crossbar not long afterwards - although the defender may have strayed just offside from John Fleck's free-kick.
United enjoyed over 60% possession in the second half but failed to test Forster again until half-time substitute Oliver McBurnie headed straight at the keeper eight minutes from time.
Wilder has always insisted his side will fight tooth and nail in their battle to avoid relegation, but time is running out for the Blades in their bid to secure a third successive season of Premier League football.
Most defeats in 15 years - the stats
- Sheffield United have become only the second English top-flight team to lose 22 of their first 28 games in a season after Sunderland in 2005-06.
- The Blades have shipped the first goal in 21 Premier League games this season - more than any other side.
- Southampton have won four consecutive league encounters with Sheffield United for the first time since 1950 in the second tier.
- Southampton ended a seven-match winless run away from home in the Premier League (D2 L5). Saints also scored as many goals at Sheffield United as they did in their previous six on the road (2).
- Southampton striker Adams has scored four goals in his four Premier League appearances against former side Sheffield United, accounting for 44% of his total goals in the competition.
- Ward-Prowse has scored seven goals in all competitions this season, his joint best return in a single campaign for Southampton. Six of these seven goals have come from dead-ball situations (5 direct free-kicks, 1 penalty).
'We have to keep improving' - what the managers said
Southampton manager Ralph Hasenhuttl, speaking to BBC Sport: "We made finishing drills in the final session yesterday and I think it helped [Adams]. It's what you are here for as a substitute that you come on and show your qualities. He played well last year as well.
"Both strikers did a good job. Nathan Tella was the man of the match today because he was hard to defend against and always hungry for every second ball."
Sheffield United manager Chris Wilder, speaking to BBC Sport: "We didn't deserve anything from the game. They [Southampton] were better. It was a great opportunity but it's been a tough week, playing Liverpool on Sunday and then down to 10 men after 60 minutes in midweek.
"We didn't show the quality we needed to hurt them. There was nothing in the game and then it was one great ball.
"It's a brilliant finish for Che [Adams]. I'm delighted for him and I've just spoken to him. He was here as a kid and was a bit of a loose cannon then, but he has got himself forward and he is a proper centre-forward."
Southampton travel to runaway Premier League leaders Manchester City on Wednesday 10 March (18:00 GMT), while Sheffield United visit top-four hopefuls Leicester City in their next league game the following Sunday (14:00 GMT).
- 22AmpaduBooked at 31mins
- 20BogleBooked at 36mins
- 16NorwoodSubstituted forMcBurnieat 45'minutesBooked at 90mins
- 4FleckBooked at 90mins
- 24BrewsterSubstituted forSharpat 68'minutes
- 17McGoldrickSubstituted forMoussetat 58'minutes
- 4VestergaardBooked at 90mins
- 17S ArmstrongBooked at 71mins
- 19MinaminoSubstituted forDjenepoat 88'minutes
- 9IngsSubstituted forAdamsat 13'minutes
- 23TellaBooked at 59minsSubstituted forRedmondat 77'minutes
- Paul Tierney
- Shots on Target
Second Half ends, Sheffield United 0, Southampton 2.
Foul by Oliver McBurnie (Sheffield United).
Ryan Bertrand (Southampton) wins a free kick in the defensive half.
Ethan Ampadu (Sheffield United) wins a free kick in the defensive half.
Foul by Che Adams (Southampton).
Jannik Vestergaard (Southampton) is shown the yellow card.
Oliver McBurnie (Sheffield United) is shown the yellow card.
John Fleck (Sheffield United) is shown the yellow card for a bad foul.
Foul by John Fleck (Sheffield United).
Che Adams (Southampton) wins a free kick in the defensive half.
Jayden Bogle (Sheffield United) wins a free kick in the defensive half.
Foul by James Ward-Prowse (Southampton).
Substitution, Southampton. Moussa Djenepo replaces Takumi Minamino.
Foul by Jayden Bogle (Sheffield United).
Ryan Bertrand (Southampton) wins a free kick in the defensive half.
Foul by Jan Bednarek (Southampton).
Billy Sharp (Sheffield United) wins a free kick in the defensive half.
Offside, Sheffield United. Ethan Ampadu tries a through ball, but Lys Mousset is caught offside.
Attempt saved. Oliver McBurnie (Sheffield United) header from the centre of the box is saved in the top centre of the goal. Assisted by John Fleck with a cross.