The 30-year-old forward featured as a second-half substitute in Newcastle's 5-0 away defeat at Manchester City - his first outing for the Magpies since sustaining an injury in a 1-1 home draw against Manchester United - and leads the line in place of Chris Wood along with captaining the hosts at St. James' Park.
The Coventry-born striker is one of two changes from Newcastle's heavy loss against Pep Guardiola's side as centre-back Fabian Schär returns to the starting line-up, replacing Jamaal Lascelles.
Martin Dúbravka continues in-between the sticks behind a four-man defence containing Emil Krafth, Schär, Dan Burn and Matt Targett.
Bruno Guimarães maintains his spot in the middle of the park along with fellow Brazilian Joelinton, who was named as the club's 2021/22 Player of the Season, and Sean Longstaff.
Miguel Almirón and Allan Saint-Maximin are likely to provide support on the respective wings for Wilson.
Eddie Howe has attacking options to deploy from the bench, including Dwight Gayle, Jacob Murphy, Ryan Fraser and Matt Ritchie, who scored the winner in Newcastle's last victory over Arsenal - a 2-1 triumph back in April 2018.
Kieran Trippier, like Wilson, made his long awaited return to the side as a substitute against Manchester City and is also named on the bench along with Federico Fernández and Paul Dummett.
Newcastle United: Martin Dúbravka, Emil Krafth, Fabian Schär, Dan Burn, Matt Targett, Bruno Guimarães, Sean Longstaff, Joelinton, Miguel Almirón, Allan Saint-Maximin, Callum Wilson.
Substitutes: Karl Darlow, Kieran Trippier, Jamaal Lascelles, Federico Fernández, Paul Dummett, Matt Ritchie, Ryan Fraser, Jacob Murphy, Dwight Gayle.