Stuart Armstrong gave the hosts the lead in the first half before Chris Wood headed in his first goal for Newcastle to draw the sides level going in at half-time.
Full debutant Bruno Guimaraes put The Magpies in front with a stunning back-heel volley to secure three points.
Our writer Dominic Scurr has dished out his player ratings from the the match…
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1. Martin Dubravka - 8
Made a smart stop to deny Borja in the first half. Could do little about the goal but made a great save to deny Salisu in the final minute of normal time. Photo: Shaun Botterill
2. Emil Krafth - 6
Got stuck in down the right side but also let Southampton in on occasion. Photo: Stu Forster
3. Fabian Schar - 7
Played on despite going down twice. Had a good chance to extend Newcastle's lead in the second half. Photo: Stu Forster
4. Dan Burn - 8
Nodded the ball back across goal for Bruno to put Newcastle in front. Made some important blocks at the other end. Photo: George Wood