Max Allegri drops Federico Chiesa and Matthijs de Ligt in favour of Dejan Kulusevski and Giorgio Chiellini, as Juventus face Edin Dzeko and Lautaro Martinez’s Inter.
The Derby d’Italia kicks off at San Siro at 19.45 UK time (18.45 GMT).
This is a showdown between the reigning Scudetto holders and the previous incumbents of that throne, who won the title nine years in a row.
Both had a mixed bag so far this season in Serie A, so this is considered a crossroads for their campaigns.
Allegri had Paulo Dybala available back on the bench after a muscular problem, but Moise Kean and Adrien Rabiot missed out.
He surprisingly chose to drop Chiesa and De Ligt, the two most valuable players in the squad on the transfer market, for Kulusevski and Chiellini.
Inter are still smarting after their 3-1 defeat to Lazio, but got back on track midweek in the Champions League against Sheriff.
The only doubt was around Hakan Calhanoglu in midfield, but Arturo Vidal is not even on the bench after coming down with flu symptoms.
Edin Dzeko and Lautaro Martinez lead the attack, as the two teams both set out in a 3-5-2 formation.
Inter: Handanovic; Skriniar, De Vrij, Bastoni; Darmian, Barella, Brozovic, Calhanoglu, Perisic; Dzeko, Lautaro Martinez
Juventus: Szczesny; Danilo, Bonucci, Chiellini; Cuadrado, Bernardeschi, Locatelli, McKennie, Alex Sandro; Kulusevski, Morata