Unbeaten across their last 55 midweek Premier League outings (W47, D8), City unsurprisingly started on the front foot against the Cottagers, with Phil Foden twice going close to a breakthrough inside the opening 10 minutes.
The hosts continued to threaten as the first half progressed, and their pressure was duly rewarded in the 24th minute when a poor defensive header from Sander Berge allowed Antoine Semenyo to clinically convert his 13th league goal of the season.
Fulham went close to an immediate response, with Harry Wilson seeing a low effort thwarted by Gianluigi Donnarumma, and that save proved to be crucial as City doubled their lead on the half-hour mark.
Semenyo was involved once again, threading an inch-perfect ball into the path of Nico O'Reilly, who held his nerve to finish expertly beyond Bernd Leno.
Armed with all the momentum, the hosts added a third before half-time, as Erling Haaland swept a trademark finish into the bottom corner from outside the box.
Having found the net in 13 of their last 14 top-flight matches, Fulham tried to gain a foothold in the contest at the start of the second period, with Emile Smith Rowe and Raul Jimenez failing to hit the target with a couple of half-chances.
City, however, remained in cruise control with time ticking into the final half-hour, and Pep Guardiola reacted by using the opportunity to rest several of his key players.
Ultimately, the match fizzled out, as despite some late pressure from the visitors, City cruised through the closing stages to extend their unbeaten league run on home soil to 12 matches (W10, D2), and keep the pressure firmly on Arsenal at the summit.
Flashscore Man of the Match: Antoine Semenyo (Manchester City)