Mikel Merino, Christian Atsu and Jacob Murphy have been recalled by Rafa Benitez at Anfield.
Newcastle take on third-placed Liverpool in a televised game (5.30pm kick-off).
Merino replaces the injured Jonjo Shelvey in midfield, while Murphy and Atsu come in for Matt Ritchie and Ayoze Perez, who drop down to the bench.
Atsu will play in the No 10 role behind Gayle.
United dropped down to 16th place in the Premier League after this afternoon's fixtures.
Fourth-placed Liverpool can move up to second with a win over Newcastle.
Former United midfielder James Milner is on the bench for Jurgen Klopp's side.
NEWCASTLE UNITED: Dubravka; Yedlin, Lascelles, Lejeune, Dummett, Murphy, Diame, Merino, Kenedy, Atsu, Gayle. Subs: Darlow, Manquillo, Clark, Hayden, Ritchie, Perez, Joselu.
LIVERPOOL: Karius, Alexander-Arnold, Lovren, Van Dijk, Robertson, Henderson, Can, Oxlade-Chamberlain, Salah, Mane, Firmino. Subs: Mignolet, Milner, Gomez, Moreno, Lallana, Solanke, Matip.