Milan give a surprise start to Rafael Leao with Suso and Krzysztof Piatek, while Inter use Lautaro Martinez with Romelu Lukaku.
The Derby della Madonnina kicks off at 19.45 UK time (18.45 GMT).
Marco Giampaolo’s Rossoneri are coming off two unconvincing victories against Brescia and Hellas Verona, with Davide Calabria suspended and Mattia Caldara injured.
It means Andrea Conti makes his first appearance at right-back, his first start since April 28 in a 2-0 defeat to Torino.
Lucas Biglia again gets the nod in midfield rather than summer signing Ismael Bennacer, with Hakan Calhanoglu and Franck Kessie completing the old guard.
While people thought it was between Ante Rebic and Lucas Paqueta for a starting spot, both are surprisingly benched in favour of Portuguese 20-year-old Rafael Leao.
He only has one appearance for Milan, a 15-minute substitute run-out in the season opener against Udinese on August 25.
Suso goes into the trequartista role, supporting Krzysztof Piatek.
Inter have a 100 per cent Serie A record under Antonio Conte, but were held to a 1-1 midweek Champions League draw by Slavia Prague in this stadium.
Romelu Lukaku has shaken off a back problem and is partnered by Lautaro Martinez, despite reports Stefano Sensi would be moved into a more advanced supporting role with Matteo Politano.
Sensi remains in midfield with Nicolò Barella and Marcelo Brozovic, while Danilo D’Ambrosio comes in for not fully fit Antonio Candreva.
Diego Godin returns after he was rested in the Champions League.
Alexis Sanchez remains on the bench as a card to be played in the second half.
Milan: G Donnarumma; Conti, Musacchio, Romagnoli, Rodriguez; Kessie, Biglia, Calhanoglu; Suso, Piatek, Leao
Milan bench: Reina, A Donnarumma, Theo Hernandez, Duarte, Bennacer, Gabbia, Borini, Bonaventura, Paqueta, Rebic, Castillejo, Krunic
Inter: Handanovic; Godin, De Vrij, Skriniar; D’Ambrosio, Barella, Brozovic, Sensi, Asamoah; Lautaro Martinez, R Lukaku
Inter bench: Padelli, Ranocchia, Dimarco, Bastoni, Gagliardini, Vecino, Lazaro, Borja Valero, Biraghi, Candreva, Alexis Sanchez, Politano
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