Welbeck has been in a rich vein of scoring form recently, netting twice against Southampton and once in the Europa League encounter with CSKA Moscow, but makes way for the two most expensive signings in Arsenal's history.
Teenager Joe Willock makes his first Premier League start for the Gunners in midfield while Rob Holding and Calum Chambers come in as Arsene Wenger rests Laurent Koscielny and Hector Bellerin.
Wenger has included Reiss Nelson and Eddie Nketiah on the substitutes bench with Danny Welbeck also available to be called upon following his goal against CSKA Moscow on Thursday.
Newcastle start with their in-form attacking trio of Kenedy, Perez and Dwight Gayle as Rafa Benitez's side look for their fourth consecutive league victory.
Arsenal team: Cech; Chambers, Mustafi, Holding, Monreal; Elneny, Xhaka, Willock; Iwobi, Aubameyang, Lacazette. Subs: Ospina, Maitland-Niles, Mertesacker, Kolasinac, Nelson, Welbeck, Nketiah
Newcastle team: Dubravka; Yedlin, Lascelles, Lejeune, Dummett; Ritchie, Shelvey, Diame, Kenedy; Perez, Gayle. Subs: Darlow, Clark, Manquillo, Hayden, Murphy, Slimani, Joselu