The Magpies saw a goal controversially disallowed in the first-half at St Mary's Stadium as Joelinton's close-range volley was adjudged to strike the Brazilian's arm in the build-up but the South American midfielder was later on hand to convert in the closing stages of the last four tie, firing home from close-range following Alexander Isak's impressive assist.
Adam Armstrong, who began his playing career at Newcastle, looked to have swiftly drawn the hosts level but the former Magpie's effort was ruled out for handball after a VAR review before Southampton defender Duje Ćaleta-Car was sent off in the latter stages after receiving two bookable offences.
Eddie Howe named an unchanged starting XI from the side which claimed a goalless draw away at Crystal Palace last weekend ahead of the Magpies' first cup semi-final since 2005 in the FA Cup and had already defeated Southampton on away soil in November, gaining an 4-1 victory on the South coast.
The Magpies, backed by 3,200 travelling away supporters, almost got off to a positive start inside the opening 120 seconds as Callum Wilson's neat pass from Kieran Trippier's throw-in set Miguel Almirón on his way towards goal before the Paraguyan picked out Joe Willock but the 23-year-old midfielder fired an effort over the crossbar.
In a first-half contest lacking a vast amount of clear-cut goalscoring opportunities, Willock missed another chance in front of goal after connecting with Kieran Trippier's lofted cross from the right wing but the following attempt at goal was directed wildly over the bar.
Joelinton looked to have sent United in front before the break as the Brazilian volleyed the ball into the net from close-range after Willock's low shot was parried by Saints goalkeeper Gavin Bazunu but, as Callum Wilson's scrambled rebound was blocked by Saints defender Mohammed Salisu, referee Stuart Attwell adjudged the loose ball to have struck Joelinton's arm before rifling home.
Pope, targeting a tenth consecutive clean sheet across all competitions, denied Carlos Alcaraz from distance after the Argentine's strike landed awkwardly in front of the England international, who pushed the ball away from safety.
Newcastle began the second-half in bright fashion as Almirón darted down the left wing before finding Longstaff on the edge of the penalty area but the midfielder fired wide of the target.
Joelinton spurned a glorious opportunity to break the deadlock after Almirón's pass across the face of goal found its way to the Brazilian but his close-range effort was lashed over the bar to the disbelief of the away supporters.
Sven Botman went close to recording his first goal for the club since arriving from Lille last summer as the Dutch defender latched onto a loose ball inside the box as Bazunu parried Almirón's cross-cum shot but the centre-back's strike hit the side-netting.
Pope produced two important stops to keep United on level terms after the Soham-born shot-stopper denied Saints substitute Ché Adams on both occasions, the first a strong block with his leg after the striker raced through on goal before denying the Scotsman minutes later, who swivelled inside the box before firing towards goal.
In the 73rd minute, Newcastle took the lead through Joelinton. After Isak brilliantly evaded Ćaleta-Car on the right flank, the Swedish substitute played the ball expertly into the Brazilian's path who comfortably placed the ball into the net.
It looked as if United's one-goal cushion was quickly distinguished as Armstrong bundled the ball home after the Newcastle defence failed to clear the ball to safety but replays showed the ball to clip the Saints striker's hand, with Attwell subsuquently ruling out the effort.
Southampton were reduced to ten men in the final minutes of the first leg as Ćaleta-Car picked up his second yellow card of the night, tripping Allan Saint-Maximin as the French substitute advanced dangerously past the Croatian defender.
Newcastle take on Southampton in seven days' time for a highly-anticipated second leg at St. James' Park as the Magpies, unbeaten on home soil since April 2022, bid to claim a positive result to end a 24-year wait for a longly awaited cup final appearance at Wembley Stadium.
