Manager Gareth Taylor said in the build-up to the game that he thought City were good enough to win the competition and they raced into an early lead against their Italian opponents, with Lauren Hemp and Ellen White scoring inside the opening four minutes.
Fiorentina, who were last season’s Serie A runners-up, lost 6-0 on aggregate to Arsenal in the competition last year and looked on course for a similarly heavy defeat in Manchester, but they were able to limit City’s advantage after their initial dominance.
The Viola are the last remaining Italian side in the tournament following Juventus’ exit to last year’s champions Lyon, but any hopes of progressing were further dented when Sam Mewis came off the bench to head home a third.
City took the lead after two minutes when Chloe Kelly drove down the right and crossed for Hemp, who made no mistake to open the scoring.
Taylor’s side did not have to wait long for a second, with Hemp turning provider down the left for White to tap home two minutes later.
Scotland international Caroline Weir came close to adding a third, forcing Fiorentina goalkeeper Katia Schroffenegger to come off her line and punch.
Fiorentina had a chance to snatch a crucial away goal at the start of the second half when substitute Lana Clelland played in Frederikke Thogersen but the Danish forward rushed her shot and curled the ball away from goal.
City added a third in the 89th minute when Kelly provided another assist, this time for Mewis, who headed past the keeper at the far post.