Graziano Pellè scored a dramatic late winner to earn Saints a 3-2 win against Stoke City and book their place in the Capital One Cup quarter-finals.
The hosts had fought back from 2-0 down to level with just under ten minutes remaining, but following a red card to former Saints striker Peter Crouch, Pellè pounced to send Saints through.
Pellè had earlier grabbed his eighth goal of the season with a superbly taken strike from 25 yards to hand Ronald Koeman’s side the lead, before Shane Long got off the mark for the club following his move in the summer.
The former Hull City striker put the finishing touches to a flowing team move down Saints’ right-hand side on the half-hour mark to make it 2-0.
Stoke City reduced the deficit right at the start of the second half, with Steven N’Zonzi striding forward and finding the bottom corner with a powerful low drive, before Mame Biram Diouf nodded home to equalise with eight minutes of normal time left.
Crouch was then shown a second yellow card in just a matter of minutes and from the resulting free-kick Pellè connected with a loose ball to smash home the winner.
The victory for Koeman’s side means they will compete in the last eight of the Capital One Cup for the first time since the 2003/04 campaign.
Koeman made four changes from the weekend win against the Potters, with Florin Gardoș, Matt Targett, Victor Wanyama and Long coming into the team to replace Toby Alderweireld, Ryan Bertrand, Jack Cork and Sadio Mané.
The changes meant Saints went with a 4-4-2 formation, with Steven Davis playing on the right of midfield and Long joining Pellè in attack.
For the hosts, there were three changes from Saturday, with Crouch dropping to the bench in place of Diouf, while Bojan and Marko Arnautovic came in for Charlie Adam and Victor Moses.
Koeman said before kick-off that he expected a reaction from the Potters following Saints’ 1-0 win at St Mary’s in the league on Saturday, but it was his side who were on the front foot right from the off, and took the lead with just six minutes gone.
Targett, making only his third start for the club, drove forward and played a neat ball inside to Pellè who turned into space and curled his shot brilliantly past Potters goalkeeper Asmir Begovic from 25 yards.
Despite the home side having a spell of pressure, Saints were looking a threat every time they went forward, and they soon doubled their lead following an excellent team move.
Dušan Tadić played a reverse pass into Davis who cut the ball back to the penalty spot where Long was waiting to pass through the legs of Begovic and get his first goal in a Saints' shirt.
It was almost 3-0 moments later as Tadić clipped a clever ball into the path of Pellè, who turned away from his man but fired over the bar from 12 yards.
The two-goal lead was to be halved right at the start of the second half, with N’Zonzi firing home a low drive from distance that found the bottom corner.
As the home side pushed on in search of a quickfire second, Saints were able to find space in behind, and almost regained their two-goal advantage through Long.
Tadić picked out the striker but Begovic was off his line sharply to block Long’s effort and turn it behind.
The goalkeeper was on hand again moments later to deny Wanyama after a clever interchange between the midfielder and Tadić.
The home side pressed in search of an equaliser, sending on Crouch and Adam with just over 15 minutes to go, and they drew level when the latter’s corner was flicked on and headed home by an unmarked Diouf from six yards.
It looked as though it was heading for extra time, but after Crouch was shown two yellow cards for two poor tackles within a minute, Saints snatched a late winner.
From the resulting free-kick after Crouch had fouled Davis to be given his marching orders, the ball broke kindly for Pellè who smashed home instinctively on the turn.
The ten men tried to find a second equaliser but despite six mintues of additional time, Saints held on to progress to the last eight for the first time in 11 seasons.
Stoke City: Begovic, Bardsley, Shawcross (c), Wilson, Pieters, Cameron (Adam 73), N’Zonzi, Walters, Bojan (Crouch 73), Arnautovic, Diouf.
Unused Substitutes: Sorensen (GK), Muniesa, Ireland, Sidwell, Assaidi.
Goals: N’Zonzi (48), Diouf (83)
Booked: Bardsley (64), Wilson (66), Adam (76), Crouch (87)
Sent Off: Crouch (88)
Southampton: Forster, Clyne, Fonte, Gardoș (Alderweireld 90), Targett, Wanyama, Schneiderlin, S. Davis (Cork 90), Tadić, Long, Pellè.
Unused Substitutes: K. Davis (GK), Reed, Mayuka, Bertrand, Yoshida.
Goals: Pellè (6, 88), Long (30)
Booked: Fonte (87), Pelle (89)
Referee: Lee Mason
Attendance: 16,340, (2,193 Saints fans)