Nathan Jones's side stunned perennial champions Manchester City to make it to the final four, while the Magpies confidently dispatched Leicester City 2-0, and the two hopefuls will face off again on January 31 for the chance to meet Manchester United or Nottingham Forest in the showpiece match.
Match preview
What could have been the catalyst for an improved run of fortunes at St Mary's has not quite panned out that way for Southampton, who have been brought crashing back down to earth since their shock elimination of Man City in the EFL Cup quarter-finals.
A comeback victory over fellow Premier League strugglers Everton last weekend continued to brighten the mood, but there was little joy to be had at St Mary's on Saturday, where Ollie Watkins scored the only goal of the game in a 1-0 success for Aston Villa after a drone had halted play.
Referee Michael Salisbury was the target of Saints' frustrations after another goal for captain James Ward-Prowse was ruled out, with Mohamed Elyounoussi adjudged to have fouled Jacob Ramsey, leaving the South Coast side rock bottom of the Premier League table.
The cups have been a welcome distraction for the Saints, though, as Jones's side previously saw off Cambridge United, Sheffield Wednesday and Lincoln City to make it this far and are now bidding to reach their first final since 2016-17, where they ultimately lost to Jose Mourinho's Manchester United.
Somewhat bizarrely, Man City are the only team to have failed to score at St Mary's in Southampton's last 15 home matches, but Newcastle have hardly been ruthless in front of goal during the period of cold snaps.
It took an 89th-minute header from Alexander Isak to help Newcastle see off Fulham last weekend, but they were met with another low block in the form of Crystal Palace on Saturday, and Howe's men would not find their way through this time around.
While Vicente Guaita came up with seven saves at Selhurst Park - albeit mostly comfortable ones - Nick Pope was called into action to produce a sensational stop from Jean-Philippe Mateta, and that point was enough for Newcastle to rise to third before Manchester United's meeting with Arsenal.
A hint of apprehension may be creeping in for Newcastle fans after witnessing their side score just four goals in their last six games, although two of those came in their quarter-final win over Leicester, where second-half strikes from Joelinton and Dan Burn did the damage.
Competing in the EFL Cup semi-finals for the first time since the 1975-76 season - their only appearance in the final four to date - Newcastle travel to St Mary's having failed to win any of their three away games so far in 2023, but goals against Southampton have been easy to come by for the Magpies.
Indeed, Howe's side stormed to a 4-1 win at St Mary's earlier this season - their third triumph from their last four over Southampton - and they have struck 11 goals versus the Saints in that time, albeit while conceding six themselves.
Southampton EFL Cup form:
W
W
W
W
Southampton form (all competitions):
L
L
W
W
W
L
Newcastle United EFL Cup form:
W
W
W
W
Newcastle United form (all competitions):
D
D
L
W
W
D
Team News
A quintet of players missed out for Southampton at the weekend, with Juan Larios and Valentino Livramento both guaranteed to sit this one out too, and it remains to be seen if Alex McCarthy, Theo Walcott and Armel Bella-Kotchap can shake off their concerns in time for Tuesday.
Jones is facing some crucial decisions in the final third, as Sekou Mara and Moussa Djenepo - who both started on the bench at the weekend - came up with the goals that dumped Man City out of the EFL Cup in the quarter-finals.
No player has scored more EFL Cup goals than Che Adams's four this term, but another uninspired outing against Villa means that his spot is certainly under threat from Mara.
As for Newcastle, Bruno Guimaraes somehow completed the full 90 minutes at Selhurst Park, despite suffering a serious-looking ankle injury against Fulham last weekend, and he will seemingly be fine to start again after coming through unscathed.
Jonjo Shelvey, Matt Targett and Emil Krafth remain out of contention for the Magpies, who should keep changes to a minimum for this encounter, but Howe will surely be tempted into an attacking switch or two.
Isak and Allan Saint-Maximin are ready to provide some fresh legs in the final third, with Callum Wilson possibly fearing for his place after going eight games without finding the back of the net.
Southampton possible starting lineup:
Bazunu; Lyanco, Salisu, Caleta-Car, Walker-Peters; Diallo, Lavia; Edozie, Ward-Prowse, Djenepo; Mara
Newcastle United possible starting lineup:
Pope; Trippier, Schar, Botman, Burn; Willock, Guimaraes, Longstaff; Almiron, Isak, Joelinton
We say: Southampton 0-2 Newcastle United
Southampton will give themselves the best possible chance of a positive first-leg result if they set up to frustrate Newcastle, who have hardly been clinical in front of goal recently, but Jones may opt to go gung-ho at home before a more conservative approach at St James' Park.