For Saint-Maximin, it is a first start since mid-November, the Frenchman having been injured over the Christmas before making his return as a substitute against Aston Villa last month.
Willock, meanwhile, linked up with the club on loan from Arsenal earlier this week, and goes straight into Steve Bruce’s side as the Magpies target an important win against a Saints outfit who lost 9-0 to Manchester United on Tuesday.
The pair come in for Ryan Fraser and Ciaran Clark, the former making today’s bench while the latter misses out entirely through injury.
Otherwise, the Magpies are unchanged from the team beaten 2-1 by Crystal Palace four days ago. Karl Darlow keeps his place between the sticks, with Isaac Hayden dropping back into central defence to fill the void left by Clark. He joins Fabian Schär, Jamal Lewis and Javier Manquillo at the back.
Willock plays alongside Jeff Hendrick and stand-in skipper Jonjo Shelvey in central midfield, with Saint-Maximin and Miguel Almirón providing support to Callum Wilson up top.
Bruce has a wealth of attacking options on the bench, including frontmen Joelinton, Andy Carroll and Dwight Gayle.
Newcastle United: Karl Darlow, Javier Manquillo, Isaac Hayden, Fabian Schär, Jamal Lewis, Jeff Hendrick, Jonjo Shelvey, Joe Willock, Miguel Almirón, Allan Saint-Maximin, Callum Wilson.
Substitutes: Martin Dúbravka, Emil Krafth, Paul Dummett, Matt Ritchie, Ryan Fraser, Elliot Anderson, Joelinton, Andy Carroll, Dwight Gayle.