The Fulham captain was dismissed after just six minutes at the Etihad Stadium, effectively ending any hopes the Championship side might have had of upsetting the holders.
Ilkay Gundogan put City ahead from the penalty spot after Ream's foul before Bernardo Silva added a second and Gabriel Jesus struck twice in the second half.
City may be out of Premier League title contention but they have no intention of giving up either of the other two domestic trophies they won last season easily.
Their goals took their tally to the season in all competitions to 102 and put them in good heart for the second leg of their Carabao Cup semi-final against Manchester United in midweek.
City made eight changes, naming the likes of Raheem Sterling, Sergio Aguero and Kevin De Bruyne on the bench, but were still far too strong for Fulham.
Yet the visitors contributed to their own downfall with a number of mistakes, not least Ream's disastrous early intervention.
Jesus was played through by Gundogan but before the Brazilian could shoot he was pulled back from the shoulder by Ream. Referee Kevin Friend immediately pointed to the spot and brandished the red card.
Gundogan rolled the penalty into the bottom corner and City piled on the pressure with Angelino, Riyad Mahrez and Phil Foden all going close.
The inevitable second goal came after 19 minutes. At first it seemed the chance may have gone for Bernardo Silva as he was forced out of the area but his footwork tricked the defenders. He created space with a smart turn and then clipped a shot into the bottom corner, registering City's 100th goal of the season in the process.
City then eased off the gas but Fulham were almost caught out again by another break and Joe Bryan resorted to a cynical foul to halt a Mahrez charge.
Mahrez fired over early in the second half and was taken off soon afterwards, perhaps to get some rest ahead of Wednesday's derby.
But there was no respite for Fulham as Sterling came on to replace him and struck the bar within minutes of coming on after being played in by David Silva.
David Silva then set up Jesus but Terence Kongolo, making his Fulham debut after moving on loan from Huddersfield, denied him with a fine tackle.
While that was a good moment for Kongolo, he had one to forget in the 72nd minute when he was dispossessed by Bernardo Silva. The ball was worked back to Joao Cancelo and his precise cross was headed firmly home by Jesus.
Fulham made almost the same mistakes again moments later, this time Michael Hector gifting the ball to Jesus. He played in Foden, whose shot was saved by Marek Rodak, but the Brazilian followed up to head in from close range and complete the job.