Goals from William Carvalho, Goncalo Guedes, Cristiano Ronaldo and Bernardo Silva put Portugal second in Group B on five points from three games.
Manchester City remain on course for an unprecedented quadruple of Premier League, Champions League, FA Cup and League Cup.
Manchester City suffered a shock 1-2 home defeat to Lyon in their opening Champions League 2018/19 match.
Bernardo Silva's fine finish capped a typically incisive City raid that suggested Pep Guardiola's side have picked up where they left off.
Two goals from substitute Bernardo Silva helped Manchester City come from 2-0 down to end a run of two defeats in this International Champions Cup campaign with youngster Lukas Nmecha scoring in between.
Bernardo Silva scored the only goal of the match 35 seconds into the second half at the Etihad Stadium when he prodded home at the back post from David Silva's low cross.