League One side Orient threatened to pull off a famous upset on Saturday when they led 1-0 at halftime against Pep Guardiola's four-time defending Premier League champions.
But City fought back after the break with goals from substitutes Abdukodir Khusanov and De Bruyne.
Orient went ahead in spectacular fashion when Jamie Donley's shot from just past the halfway line hit the bar and rebounded off the back of City goalkeeper Stefan Ortega into the back of the net in the 16th minute at Brisbane Road.
It was officially credited as an own goal, but Donley took all the congratulations as he celebrated wildly in front of the home fans. He was also rewarded later with the player-of-the-match award.
But the goal wasn't enough to hold off City's seemingly inevitable fightback.
Rico Lewis's effort deflected of Khusanov in the 56th to level the match before De Bruyne, who'd only been on the pitch for a few minutes, raided brilliantly to flick a shot past Josh Keeley in the 79th minute to seal victory.
It wasn't all good news for Guardiola, though, with expensive new midfield signing Nico Gonzalez injured and substituted after 22 minutes of his debut.
The midfielder, who joined from Porto for a reported $A98.6 million on transfer deadline day, appeared to hurt his ribs after falling awkwardly in a challenge with Orient's Sonny Perkins.
After receiving treatment, Gonzalez held his side as he left the field early and his injury will be a concern for Guardiola ahead of Tuesday's Champions League play-off against Real Madrid.
