The England midfielder missed last weekend's 2-0 defeat at Liverpool with a knee problem, but returned to training in midweek and will line up against the Saints at St James' Park.
Southampton, meanwhile, make two changes from the side that drew 0-0 with Stoke City last week.
Newcastle United: Dubravka; Yedlin, Lascelles, Lejeune, Dummett; Ritchie, Shelvey, Diame, Kenedy; Perez, Gayle
Subs: Darlow, Clark, Murphy, Manquillo, Joselu, Merino, Atsu
Southampton: McCarthy; Soares, Stephens, Hoedt, Bertrand; Lemina, Hojbjerg; Redmond, Ward-Prowse, Tadic; Carrillo
Subs: Forster, Long, Romeu, Boufal, Gabbiadini, Bednarek, Sims