Romelu Lukaku netted a late winner to cruelly deny Southampton what would’ve been a valuable point towards their fight for Premier League survival.
The forward, who scored twice, struck a right-footed effort past Angus Gunn in the 88th minute of a 3-2 win for Manchester United at Old Trafford.
Each team had fought back from a goal deficit, with James Ward-Prowse scoring a sublime free-kick to draw Southampton level at 2-2 with 15 minutes remaining.
Southampton is winless in their last six attempts against Manchester United (3D, 3L), which includes the latest defeat.
Despite the result, Saints are bolstered by the fact they remain above the drop by two points with Cardiff City having lost 2-0 at Wolverhampton.
United failed to make use of a spirited start, as goalkeeper Angus Gunn backstopped an early onslaught of chances and twice denied Lukaku in the opening five minutes.
Yan Valery then produced a bit of magic for his first senior goal in the way of right-footed drive that beat David De Gea into the top corner.
Southampton would be unfortunate to not be awarded a pair of penalties in the opening half, with Bertrand being taken down in the area either side of the opening goal.
Andreas Pereira matched Valery’s effort, firing United back into the match with an attempt from 25 yards out that reached the top corner.
Lukaku then pushed United in front five minutes later after finding the far bottom corner from just inside the box.
Ward-Prowse, who has surged into form under Ralph Hasenhuttl, brought Southampton level as he sent a free-kick from 25 yards out over the wall and into the top corner.
But the late drama turned on its head for Southampton when Lukaku added his second of the afternoon to give United a 3-2 lead.
Southampton gave away a late penalty when substitute Stuart Armstrong was adjudicated to have brought Marcus Rashford down, but Gunn was equal to the task to prevent final result from widening.
Manchester United: De Gea, Shaw, Lindelof, Smalling, Young, Pogba, McTominay, Pereira (Fred 82), Sanchez (Dalot 52), Lukaku, Rashford (Chong (90+5).
Unused subs: Grant (GK), Rojo, Bailly, Gomes.
Goals: Pereira (53), Lukaku (59, 88),
Bookings: Lukaku (89), Pogba (90+6).
Southampton: Gunn, Bertrand, Vestergaard, Yoshida (Gallagher 90), Bednarek, Valery, Hojbjerg, Romeu, Ward-Prowse, Austin (Armstrong 63), Redmond.
Unused subs: McCarthy (GK), Stephens, Elyounoussi, Targett, Slattery.
Goals: Valery (26), Ward-Prowse (75).
Bookings: Bertrand (39),