The striker could make his debut after signing in a £63.5m deal from Sporting, but Kai Havertz starts up front instead, with Mikel Arteta making five changes from their win over Newcastle.
Jakub Kiwior replaces Riccardo Calafiori at centre-back to partner William Saliba.
Declan Rice, Christian Norgaard and Martin Odegaard start in midfield instead of Ethan Nwaneri, Martin Zubimendi and Mikel Merino.
Gabriel Martinelli comes in for Leandro Trossard on the left.
Tottenham XI: Vicario; Porro, Romero, Van de Ven, Spence; Bentancur, Sarr, Bergvall; Kudus, Richarlison, Odobert.
Arsenal XI: Raya; White, Kiwior, Saliba, Lewis-Skelly; Rice, Norgaard, Odegaard; Saka, Havertz, Martinelli.
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