With Kieran Trippier serving a one-match suspension after picking up a fifth Premier League yellow card of the season away at Tottenham Hotspur last weekend, Dan Burn has been handed his first start in the English top-flight since the Magpies' 1-0 win against Arsenal last month.
Martin Dúbravka continues in-between the sticks, with Tino Livramento expected to feature at right-back while Jamaal Lascelles and Fabian Schär continue at the heart of the Magpies backline.
Longstaff, who returned to competitive action against AC Milan in the UEFA Champions League on Wednesday after sustaining an ankle injury, replaces Lewis Miley in the middle of the park and is situated alongside Bruno Guimarães and Joelinton, with the latter set for his 150th Premier League appearance this afternoon.
Miguel Almirón and Anthony Gordon will aim to provide attacking support for frontman Callum Wilson, with the Coventry-born forward on target against the West London outfit in a 4-1 away win at Craven Cottage in October 2022.
Howe has named nine substitutes ahead of facing the Cottagers, with Sven Botman named in a United matchday squad for the first time since September.
Loris Karius and Mark Gillespie are the goalkeeping backups, while Paul Dummett, Emil Krafth and Matt Ritchie could also be deployed from the bench as well as teenage trio Lewis Hall, Alex Murphy and Miley.
Newcastle United: Martin Dúbravka, Tino Livramento, Jamaal Lascelles (c), Fabian Schär, Dan Burn, Sean Longstaff, Bruno Guimarães, Joelinton, Miguel Almirón, Anthony Gordon, Callum Wilson.
Substitutes: Loris Karius, Mark Gillespie, Emil Krafth, Paul Dummett, Sven Botman, Lewis Hall, Alex Murphy, Matt Ritchie, Lewis Miley.