With Joelinton serving a one-match suspension, after picking up a fifth yellow card of the season against Aston Villa, Murphy replaces the Brazilian in the only change from Newcastle's emphatic 4-0 win against the Villans last weekend.
Eddie Howe's side travel to the South coast aiming to extend their unbeaten Premier League run to nine matches as well as recording a fourth successive victory following triumphs over Everton, Tottenham Hotspur and Aston Villa.
Nick Pope continues in-between the sticks for the Magpies while Swiss defender Fabian Schär, making his 100th Newcastle start this afternoon, continues in the heart of the United backline alongside Sven Botman, with Kieran Trippier and Dan Burn occupying the respective flanks.
Bruno Guimarães, who scored on his full Newcastle debut away at Southampton last term, starts in the middle of the park along with Sean Longstaff and Joe Willock.
Miguel Almirón, who received a Premier League Player of the Month nomination for October after scoring six goals in six matches, will aim to maintain his eye-catching form as the Paraguyan forward provides attacking support for Callum Wilson, making his 50th start for Newcastle.
Howe has a number of options to deploy from the substitutes' bench, including Allan Saint-Maximin - who has registered two goals and two assists in his last four appearances against Southampton - as well as striker Chris Wood, who scored his first goal for Newcastle in a 2-1 away win against the Saints last term.
There is a place on the bench for Jonjo Shelvey, who will make his 200th Newcastle appearance should he feature against Ralph Hasenhüttl's side, and Elliot Anderson - who celebrates his 20th birthday today.
Karl Darlow returns to the Magpies' matchday squad for the first time since September after recovering from an ankle injury, while Jamaal Lascelles, Mattt Targett, Javier Manquillo and Ryan Fraser make up the remainder of the bench.
Newcastle United: Nick Pope, Kieran Trippier (c), Fabian Schär, Sven Botman, Dan Burn, Sean Longstaff, Bruno Guimarães, Joe Willock, Miguel Almirón, Jacob Murphy, Callum Wilson.
Substitutes: Karl Darlow, Javier Manquillo, Jamaal Lascelles, Matt Targett, Jonjo Shelvey, Elliot Anderson, Ryan Fraser, Allan Saint-Maximin, Chris Wood.
