With Jonjo Shelvey missing out due to a calf injury, Willock will get the chance to score for the eighth successive Premier League game following his stunning finish to last term. He completed a permanent move to the Magpies from Arsenal last week.
Also coming into the side are captain Jamaal Lascelles and fellow centre-back Fabian Schär, who replace Emil Krafth and former Villa man Ciaran Clark in the starting XI.
Lascelles missed the 2020/21 run-in with a foot injury, while Schär helped Switzerland reach the quarter-finals of Euro 2020 and both have therefore had somewhat disrupted pre-seasons, but Steve Bruce has now deemed them fit enough to start.
Freddie Woodman makes his second Premier League start in goal, behind a backline of Lascelles, Schär and Federico Fernández. Jacob Murphy and Matt Ritchie continue as wing-backs, with the pair combining brilliantly for United's second goal against West Ham last weekend.
Isaac Hayden will be tasked with bringing steel and discipline to the Magpies' midfield with Willock and Miguel Almirón likely to be afforded more freedom to support Allan Saint-Maximin and Callum Wilson, who got off the mark for the season after five minutes against the Hammers six days ago.
Mark Gillespie is the substitute goalkeeper, with Clark and Krafth are joined on the bench by Jamal Lewis, Jeff Hendrick, Sean Longstaff, Ryan Fraser, Dwight Gayle and Joelinton.
Newcastle United: Freddie Woodman, Jacob Murphy, Federico Fernández, Jamaal Lascelles (c), Fabian Schär, Matt Ritchie, Isaac Hayden, Joe Willock, Miguel Almirón, Allan Saint-Maximin, Callum Wilson
Substitutes: Mark Gillespie, Emil Krafth, Jamal Lewis, Ciaran Clark, Jeff Hendrick, Sean Longstaff, Ryan Fraser, Joelinton, Dwight Gayle