City's victory extended European clubs' domination of the competition since 2012 and was never in doubt once Julian Alvarez opened the scoring inside the first minute.
Nino's first-half own goal realistically ended the Brazilians' dreams of an upset, before Phil Foden and Alvarez rounded off the scoring in the final 20 minutes.
RODRI INJURY:
Fluminense were then dealt the killer blow when captain Nino turned Foden's cross into his own net after Rodri's pass opened up the Brazilian defence.
Ederson was called into action to maintain City's two-goal lead before the break as the Brazilian international made a stunning save from Jhon Arias' header.
But his opposite number Fabio was the busier goalkeeper. The 37-year-old kept the score down and saved Fluminense's blushes.
