Mattijs De Ligt, Juan Cuadrado, Rodrigo Bentancur as well as Federico Bernardeschi entered from Juve's win over AS Roma, with Victor Osimhen and Lorenzo Insigne hauled in for Napoli.
Juventus had a chance to take the lead early on following a loose ball from a scramble in the six-yard area, but Bernardeschi hurriedly fluffed the close-range attempt.
The Old Lady fell behind on the half-hour mark as Insigne drilled a spot kick into the top corner after the Video Assistant Referee (VAR) penalised Giorgio Chiellini for a foul on Amir Rrahmani.
Napoli successfully maintained the balance of play in the remainder of the first half, whilst Juve slowly pushed to get back into the contest.
Andrea Pirlo's side issued a substitution soon after halftime with Alex Sandro introduced for Cuadrado, whilst Napoli remained unchanged.
Juventus nearly drew level after a loose ball in the centre of the area found Cristiano Ronaldo, but Napoli goalkeeper Alex Meret made a smart reaction save.
Meret was at it again before the closing period when he instinctively plucked a powerful free-kick from the cusp of the area by Federico Chiesa from nestling the top corner of the net.
Juve did have the ball in the net as Alvaro Morata tapped in a cutback inside the area past Meret, but it was disallowed for offside.
Gennaro Gattuso's side struggled to contain the Bianconeri late on, as Meret parried Morata's low shot on the turn before he smothered a header from Ronaldo to see his side to victory.