The former Arsenal man returns to the Magpies engine room for his first start since the 1-0 win over Derby County back in February.
Hayden will partner Jonjo Shelvey in the middle of the park, with Matt Ritchie and Yoan Gouffran on the right and left flanks respectively.
Ayoze Perez will provide support for lone frontman Aleksandar Mitrovic - also making his first start since February - as United go in search of another win over Leeds, having beaten them 2-0 at Elland Road back in November thanks to a Dwight Gayle brace.
Further back, Karl Darlow continues in goal, with Vurnon Anita, captain Jamaal Lascelles, Chancel Mbemba and Paul Dummett making up the back four.
And defensive reinforcements on the bench are provided by Grant Hanley and the returning DeAndre Yedlin, who is back from injury.
Goalkeeper Rob Elliot, midfielders Jack Colback and Mohamed Diame, winger Christian Atsu and forward Daryl Murphy complete the list of substitutes available to Benitez for the clash with Garry Monk's men.
Newcastle United (4-4-1-1): Karl Darlow; Vurnon Anita, Jamaal Lascelles (c), Chancel Mbemba, Paul Dummett; Matt Ritchie, Isaac Hayden, Jonjo Shelvey Yoan Gouffran; Ayoze Perez; Aleksandar Mitrovic.
Substitutes: Rob Elliot, DeAndre Yedlin, Grant Hanley, Jack Colback, Mohamed Diame, Christian Atsu, Daryl Murphy.