A Joelinton strike gave the Magpies the upper hand at the halfway point in the tie, as Eddie Howe's side vie to meet Manchester United or Nottingham Forest - most likely the former - in the final.
Match preview
Profligacy plagued Newcastle during their most recent Premier League contest, which ended in a goalless stalemate with Crystal Palace, and lightning very nearly struck twice on the South coast as Howe's men struggled to make their dominance count in the first leg.
Joelinton in particular was guilty of an atrocious miss, but the Brazilian finally got one right in the 73rd minute, tapping home from Alexander Isak's low cross before Duje Caleta-Car was given an amusing farewell by Jacob Murphy after being given his marching orders.
Putting one foot firmly in the final - where Man United will surely lie in wait for Tuesday's victors after beating Forest 3-0 in their first leg - Newcastle are inching ever closer to capping off their remarkable rise with a long-awaited major piece of silverware, which has eluded them since their 1954-55 FA Cup triumph.
A third-round elimination to Sheffield Wednesday in that competition this year means that Howe's side have had a full week to recover from their St Mary's endeavours, and they could now reach a domestic cup final for the first time since the 1998-99 FA Cup, which ended in final heartache to Manchester United.
A gap of 47 years between EFL Cup finals - with Newcastle last reaching the showpiece game in 1976 - would be the longest in history should Howe's side finish the job on Tuesday, and a run of eight consecutive clean sheets at home makes them firm favourites to do just that.
In contrast, there were no clean sheets to be had at St Mary's when Southampton welcomed fellow coastal side Blackpool for an FA Cup fourth-round tie on Saturday, but a brace from the unlikeliest of sources sealed a narrow 2-1 win and a spot in round five for Nathan Jones's crop.
Left-back Romain Perraud broke the deadlock on the 22-minute mark, firing home a sumptuous free kick before making it a double for himself in the second half, and Southampton survived a nail-biting finale after Arsenal loanee Charlie Patino pulled one back for Blackpool.
Still fighting for cup glory on two fronts this season, Southampton are now aiming to become just the third team in EFL Cup history to reach the final after losing the first leg at home, with Stoke City's winners of 1972 and Arsenal's victors of 1987 both doing so.
Most in red and white will surely make the long journey North in hope rather than expectation, though, as Southampton have kept just one clean sheet from their last 15 in all tournaments, although that did come against Manchester City earlier in the EFL Cup.
The Saints have also recorded a pair of 2-1 victories at Everton and Palace away from home in 2023, although Newcastle are unbeaten in their last six meetings with Southampton at St James' Park, but Howe's charges cannot afford to dream of Wembley too early on Tuesday.
Newcastle United EFL Cup form:
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Newcastle United form (all competitions):
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L
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W
Southampton EFL Cup form:
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L
Southampton form (all competitions):
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L
W
Team News
Newcastle did not sustain any fresh injury or suspension concerns in the first leg, so Howe should only be working without the trio of Jonjo Shelvey, Emil Krafth and Matt Targett for Tuesday's second leg.
As a result, it would not be a shock to see Howe send the same starting XI out onto the field, although Isak continues to knock on the door and can feel hopeful of breaking into the team after playing a key role in Joelinton's winner last week.
Another fruitless outing for Callum Wilson made it nine successive games without a goal for the England international, but Howe has admitted that Isak still needs to build up his match fitness in training, so another super sub outing may await the Swede here.
Southampton centre-back Caleta-Car saw red in the first leg for two yellow card offences, but the Croatian served his suspension in the FA Cup at the weekend and will be fine to return to the backline on Tuesday.
Prior to Caleta-Car's dismissal, Moussa Djenepo had to come off just before the break after being clattered by Nick Pope, and it remains to be seen if the attacker can return from concussion protocols in time to make the squad. Juan Larios, Valentino Livramento and Alex McCarthy also remain absent.
New signing James Bree is not cup-tied for Tuesday and will be eligible to make his debut, but Jones should see little reason to alter the formula that held their own in the first leg, as Gavin Bazunu, Mohammed Salisu, Carlos Alcaraz and captain James Ward-Prowse prepare for recalls.
Newcastle United possible starting lineup:
Pope; Trippier, Schar, Botman, Burn; Willock, Longstaff, Guimaraes; Almiron, Wilson, Joelinton
Southampton possible starting lineup:
Bazunu; Walker-Peters, Lyanco, Caleta-Car, Salisu; Alcaraz, Diallo; Edozie, Ward-Prowse, Orsic; Mara
We say: Newcastle United 2-0 Southampton
With just a one-goal deficit to make up against a Newcastle side who are hardly ruthless in front of goal, Jones's side are not down and out by any means, but trying to attack the Magpies' steadfast defence can be a fruitless endeavour.