The former Crystal Palace hitman scored 23 Championship goals last season but was was completely left out of the squad that played against Hellas Verona last weekend.
He has reportedly been feeling a hamstring strain with Aleksandar Mitrovic on standby to replace him against Spurs at St James’ Park.
The Serbian international has enjoyed a good pre-season and has chipped in with three goals in six games.
DeAndre Yedlin will miss the game against his former club because of a hamstring injury and new signing Mikel Merino is, like Gayle, fighting to be fit in time.
Rob Elliot will likely start in goal, while the defence will be occupied by Javier Manquillo, Florian Lejeune, Ciaran Clark and Paul Dummett.