Erling Haaland made history by becoming the fastest player to reach 50 Champions League goals, achieving the feat in just 49 appearances.
Napoli's Giovanni Di Lorenzo was sent off for fouling Haaland, a pivotal moment that shifted the game's momentum.
Kevin De Bruyne's return to the Etihad was cut short as he was substituted early by Napoli manager Antonio Conte following the red card incident.
Jeremy Doku scored City's second goal, contributing to their comfortable win and allowing key players to be rested ahead of their match against Arsenal.