Gayle fired Newcastle to the Championship title last term but has been used sparingly in the top flight.
He started yesterday's 1-0 defeat at Brighton on the bench before coming on in the second half.
Gayle will get a proper run out tonight, though, when Peter Beardsley's U23 side host Wolves.
Jack Colback, who also played in the Toon's title-winning side, is given a game having not featured for Rafa Benitez yet this term.
Henri Saivet, Rolando Aarons and England U21 goalkeeper Freddie Woodman are other familiar names in the team.
Jamie Sterry and Daniel Barlaser will play too.
The Premier League 2 will be played at St James' Park.
Benitez is likely to be watching on and could make changes to his starting line-up next weekend after Brighton beat his side yesterday.
"I feel like we did enough to get a point at least," the Spaniard said after the Amex Stadium loss. "They had some chances, we had some chances.
"We had a lot of control and chances at the end.
"I think we deserved more."
