Matthijs de Ligt and Marcus Rashford scored shortly after Andre Onana's spot-kick save to put Erik ten Hag’s Manchester United on course for a much-needed 3-0 victory at promoted Southampton.
Both sides returned from the international break in desperate need of a result as Saints sought a first point since their Premier League return against a team reeling from their humbling home loss to rivals Liverpool.
Southampton started brightly but collapsed after Onana saved Cameron Archer’s poor penalty, with De Ligt’s first United goal and Rashford’s first of the campaign knocking the stuffing out of Saints.
Alejandro Garnacho added late gloss to a win that alleviates some of the pressure on Ten Hag, who could ill afford to oversee the Red Devils’ first St Mary’s defeat since 2003 after back-to-back defeats.
United began shakily but the game changed when De Ligt headed home two minutes after Onana stopped Archer’s spot-kick, with the striker then guilty of giving Rashford too much time to strike soon after.
That period towards the end of the first half proved decisive on a day when captain Jack Stephens received a late red card for a foul on Garnacho, who scored in stoppage time.
Saints boss Russell Martin made four changes on Saturday having largely stuck with the players that earned promotion, with homegrown Tyler Dibling among those brought in.
The talented 18-year-old quickly showed United what they were up against, ghosting past Diogo Dalot at the halfway line, roaring down the right and then cutting onto his left to force Onana into a save.
Saints looked sharp against initially cumbersome United, who took 15 minutes to find their feet and saw Joshua Zirkzee stopped from prodding in by home debutant Aaron Ramsdale.
Noussair Mazraoui and Bruno Fernandes had chances as Amad Diallo impressed for the visitors, with De Ligt throwing himself in front of a Yuki Sugawara cross-shot as an open, entertaining start continued.
Lesley Ugochukwu sent a free header over before Saints had a fantastic opportunity to take the lead, with referee Chris Kavanagh pointing to the spot after Dalot’s desperate challenge on exciting winger Dibling.
After a long delay in which the VAR checked the foul was in the box, Archer stepped up and saw Onana save his poor 33rd minute penalty and weak follow-up header.
It was a huge let-off that ruthless United capitalised on two minutes later.
Ramsdale had done well to tip a 20-yard Zirkzee attempt wide but could not stop De Ligt guiding home a header when the resulting corner was played back to Fernandes to send in a cross.
Saints looked punch-drunk and fell further behind in the 41st minute.
Ramsdale spread himself to stop Marcus Rashford scoring on the break, only for the resulting corner to prove costly once again.
Diallo kept the overhit set piece alive and played back to Rashford, who was afforded too much time by Archer and sent a curling 20-yard strike beyond Ramsdale.
The Southampton goalkeeper spread himself to stop De Ligt making things worse before a break that the visitors returned from strongly as Mazraoui hit the side netting and Rashford had an attempt.
The hosts had lost their way and Ramsdale did brilliantly to tip over a 60th minute Rashford curler before Martin made a quadruple switch.
The dynamics changed slightly in Saints’ favour and Ten Hag responded with a triple change of his own, including bringing on deadline-day arrival Manuel Ugarte for his debut.
Any faint hope of the promoted hosts clawing their way back into proceedings were ended in the 79th minute as referee Kavanagh dished out a straight red card for Stephens’ poor challenge on substitute Garnacho.
Fernandes whizzed wide and substitute Taylor Harwood-Bellis impressively blocked a Zirkzee attempt, with Garnacho firing home the third they had long been threatening in stoppage time.
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