A titanic tussle at St James' Park saw nine men Newcastle hang on for a win for the ages.
It looked like it was going to be plain sailing for United as debutant Joe Willock swept home a flowing move to set the tone for an impressive bow.
Miguel Almiron - again excellent - then fired home a second to put Newcastle in control before a Takumi Minamino goal put Southampton back in the match. Callum Wilson followed Javier Manquillo off with an injury before another Almiron goal restored United's advantage.
Jonjo Shelvey spurned a chance to put Newcastle 4-1 up before James Ward-Prowse's exquisite free-kick. And when Jeff Hendrick was sent off - and Fabian Schar carried off - United were reduced to nine men.
But they bravely held on - here are Lee Ryder's player ratings.
Karl Darlow 8
Helped see the game out and made some key saves. Faced 15 goal attempts.
Javier Manquillo 7
Got at Southampton early on before afternoon was curtailed before the mid-way point of first half.
Isaac Hayden 9
A crucial role in the dying stages as he cleared the ball time after time. Made six clearances overall. Not bad for a stand-in centre-back.
Fabian Schar 7
A decent effort but ended the game carried off.
Jamal Lewis 7
Battled hard and played through the pain barrier after an injury.
Jeff Hendrick 2
You can almost forgive him for the first caution but the second was beyond stupidity. Will be a relieved man tonight.
Joe Willock 8
Couldn't ask for much more on his debut. A well-taken goal and contributed massively in midfield with a host of tackles and interceptions.
Jonjo Shelvey 6
Battled hard but his sitter could have been very costly.
Allan Saint-Maximin 9
It's frightening how much more of a side Newcastle look with him in it. Two assists and full of running.
Miguel Almiron 10
Smashed one in off a defender and scored a well-taken second. His defensive contributions and time wasting capped a man of the match display.
Callum Wilson 7
Was lively until the unfortunate injury. One disallowed before being forced off on 35 minutes.
Subs
Emile Krafth 6 (for Manquillo 24)
Also on a knife edge after yellow card. Some important clearances.
Joelinton 7 (for Wilson 35)
Made some important clearances. Ended up as makeshift wing-back.
Paul Dummett 9 (for Saint-Maximin 66)
An incredible contribution with seven clearances. Was rock solid as Newcastle went down to nine men.
