SUBSTITUTE Joe Aribo struck deep into added time to see Saints take all three points from Birmingham in a chaotic 4-3 win.
The Blues had been reduced to 10 men for the final half an hour of the contest with Saints already leading by a goal.
Koji Miyoshi opened the scoring in the first two minutes before Jay Stansfield restored the lead before half-time following Adam Armstrong's equaliser.
A double salvo from David Brooks and Che Adams put Saints in control when Dion Sanderson was then shown a straight red for a foul on the influential Will Smallbone.
However, Juninho Bacuna's equaliser against the run of play meant it required a 95th-minute winner from Aribo to snatch victory.
Russell Martin made eight changes again with recalls to the starting team for Flynn Downes, making his first appearance after three weeks out, and Brooks.
Elsewhere, the team resembled the league XI we are used to - however, Taylor Harwood-Bellis started on the right of defence again.
Birmingham City have been without manager Tony Mowbray due to illness and assistant Mark Venus is in caretaker charge of the Midlands club.
Martin anticipated this only rallying the Blues, who sat three points off the drop zone despite being unbeaten at home in 2024.
Southampton's promotion rivals Leeds United drew 1-1 with Huddersfield Town in the lunchtime kick-off - meaning there was ground to make.
It was a nightmare start, though, with Miyoshi opening the scoring in just over 60 seconds - although it looked like it could have been handball.
The Japanese took advantage of criminal space to control a ball over to Birmingham's right and fire past Gavin Bazunu.
It was almost two when a Bacuna shot off the post bounced off Bazunu and behind before Brooks volleyed over a good chance.
Saints did find the response through a brilliant team goal in 18 minutes, as Jack Stephens initiated a one-touch passage between Adams and Smallbone.
Brooks received out wide from the Scot and played in A Armstrong to go through John Ruddy's legs with a low finish.
Ruddy then denied Manning a first Saints goal when the Irishman's close-range header was brilliantly stopped after an impressive leap.
However, the Blues were ahead by halftime as Stansfield capitalised on a Jan Bednarek mis-header to race through and blast into the roof of the net.
A Armstrong hit the woodwork and Smallbone shot just wide as Saints looked for an equaliser before the half-time break.
The eventual equaliser - scored by Brooks 10 minutes into the half - kickstarted a chaotic sequence of events in Southampton's favour.
Smallbone played a simple pass to the Welshman skipped past his man to stroke a beautifully curved left-footed finish into the far corner.
Adams made it 3-2 four minutes later with Smallbone again the provider, taking a loose pass and whipping it into the back post.
Adams slipped as he controlled it but was able to regain composure and prod through the defensive crowd there to defend the initial corner.
Saints were then given a man advantage as Blues captain Sanderson was sent off - perhaps harshly - for a foul on Smallbone.
He avoided a booking for a blatant pull on Adams earlier in the tie so cannot feel too unlucky to receive marching orders.
However, Bacuna was on hand to tap into an almost empty net after Stansfield's shot cannoned off the post and restore parity with less than 15 minutes remaining.
Two chances for a reply fell to Adams in the box but it was Aribo deep into added time who would send the visiting fans into raptures.
The Nigerian was on hand to finish amongst a pile-in from a Saints corner, with Martin's side camped in the Birmingham half.
Birmingham: Ruddy; Laird, Buchanan, Sanderson, Bacuna (Roberts, 90), Myoishi (Sunjic, 80), Paik (Pritchard, 64), Dozzell (Drameh, 64), James, Stansfield (Hall, 90), Aiwu.
Unused subs: Etheridge, Hogan, Jutkiewictz, Dembele.
Booked: Miyoshi, Laird, Sunjic.
Sent off: Sanderson.
Saints: Bazunu; Harwood-Bellis, Stephens, Bednarek, Manning (Kamaldeen, 86); Downes (Rothwell, 86), Smallbone (Aribo, 70), S Armstrong; Brooks (Edozie, 64), A Armstrong, Adams (Mara, 86).
Unused subs: Lumley, Bree, Charles, Dibling.
Booked: Smallbone.
Referee: James Bell.
Attendance: 23,611
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