Twenty-goal forward Gayle has been missing for the Magpies since the 2-1 win at Brentford last month but takes his place among the substitutes at Carrow Road having returned to full fitness, while Aleksandar Mitrovic leads the line against the Canaries.
Manager Rafa Benitez has made just one change to his team from the 1-0 win at Wolves on Saturday, with Ayoze Perez replacing Mohamed Diame.
Karl Darlow starts in goal, with DeAndre Yedlin, captain Jamaal Lascelles, Ciaran Clark and Paul Dummett making up the defence.
Matt Ritchie starts on the right-hand side of midfield, with Jonjo Shelvey partnering Jack Colback in the engine room and Yoan Gouffran wide on the left.
And Mitrovic will be supported by Perez in attack as United look for their fifth league win in six in East Anglia.
Goalkeeper Rob Elliot is among the substitutes, with Jesus Gamez and Grant Hanley providing defensive reinforcements.
Isaac Hayden is also named, with Diame, Christian Atsu and Gayle completing the list of replacements.
Newcastle United (4-4-1-1): Karl Darlow; DeAndre Yedlin, Jamaal Lascelles (c), Ciaran Clark, Paul Dummett; Matt Ritchie, Jonjo Shelvey, Jack Colback, Yoan Gouffran; Ayoze Perez; Aleksandar Mitrovic.
Substitutes: Rob Elliot, Jesus Gamez, Grant Hanley, Isaac Hayden, Mohamed Diame, Christian Atsu, Dwight Gayle.