The Magpies travel to Craven Cottage aiming to move into top spot of the English top-flight with a victory against Marco Silva's side and Kieran Trippier, Lloyd Kelly, Joe Willock and Harvey Barnes replace Tino Livramento, Lewis Hall, Sean Longstaff and Jacob Murphy.
Magpies goalkeeper Nick Pope continues in-between the sticks while Fabian Schär, who marked his return to playing action after a three-match suspension with a goal against Wolverhampton Wanderers last weekend, retains his spot at the heart of United's defence alongside former Fulham centre-back Dan Burn.
Bruno Guimarães, who scored the winning goal in Newcastle's previous trip to Fulham in April, starts in the middle of the park alongside fellow Brazilian Joelinton while Willock makes his first Premier League start since United's away victory against the Cottagers in April.
Anthony Gordon and Barnes, targeting a third league goal in as many outings, will aim to provide attacking support for Swedish frontman Alexander Isak, who celebrates his 25th birthday today.
Howe has a number of options to deploy from the substitutes' bench if needed, including Italian midfielder Sandro Tonali and attacking trio Jacob Murphy, Miguel Almirón and Will Osula, awaiting a competitive debut for the Magpies.
Sean Longstaff, who has scored twice in his last three trips to Craven Cottage, is also named on the bench along with Livramento, Hall and Emil Krafth.
Martin Dúbravka, who has kept six successive clean sheets against today's opponents, is the substitute goalkeeper.
Newcastle United: Nick Pope, Kieran Trippier, Fabian Schär, Dan Burn, Lloyd Kelly, Bruno Guimarães (c), Joe Willock, Joelinton, Anthony Gordon, Harvey Barnes, Alexander Isak.
Substitutes: Martin Dúbravka, Tino Livramento, Emil Krafth, Lewis Hall, Sean Longstaff, Sandro Tonali, Jacob Murphy, Miguel Almirón, Will Osula.