Newcastle's sixth win in seven games took them above Tottenham into third for a few hours at least. Miguel Almiron continued his stunning form with a seventh goal in as many games to open the scoring in sodden conditions at St. Mary's.
The onlooking England manager Gareth Southgate then had to suffer two injury scares as Kieran Trippier required treatment on a muscle injury before Callum Wilson was replaced at half-time.
Southampton twice should have levelled as Mohammed Elyounoussi and Che Adams missed glorious chances. There was no way back for Ralph Hassenhuttl's men once Chris Wood made the most of his rare chance to impress as Wilson's replacement by curling into the far corner before Trippier set up Joe Willock to make it 3-0. Romain Perraud pulled a goal back a minute from time, but Newcastle had the final word when Bruno Guimaraes curled into the bottom corner to leave the Saints still rooted in the relegation zone.
Spurs can leapfrog the Magpies back into third should they inflict a third consecutive league defeat on Liverpool later on Sunday. Michael Olise struck the winner for Crystal Palace deep into stoppage time as a 2-1 win at West Ham lifted the Eagles up to ninth.