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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9. Ryan Fraser - 7
A quieter game compared with his recent showings but worked hard throughout and didn't give the Southampton defenders a moment's rest. Photo: Stu Forster
10. Jacob Murphy - 5
Got into some decent areas but offered little. Booked. Photo: Stu Forster
11. Chris Wood - 7
Didn't get an awful lot of service but took the opportunity when it came his way. Showed good movement and connected well with Jonjo Shelvey's ball to head in his first Newcastle goal. Well deserved. Photo: PAUL ELLIS
12. Sean Longstaff - 6
On for Bruno 66: Helped Newcastle see the game out. Photo: Stu Forster