The visitors had a big chance in the very first minute as Joe Pigott found space in the box, but flicked the ball just wide.
Then George Moncur broke with pace and cut into the box to see an effort blocked, with Ruel Sotiriou firing the rebound over.
Tom James picked out Theo Archibald to beat his man but place a shot wide of the far post on six minutes as O’s remained on top, with Pigott heading over from a James corner moments later.
Moncur’s shot from the edge of the box was deflected away from danger by Carl Johnston, before Jordan Graham found Sotiriou to tee up Idris El Mizouni, who fired over.
Archibald’s tight-angled effort was saved by Jay Lynch on 19 minutes, with James seeing a goalbound attempt superbly saved before the half-hour mark.
Sol Brynn got down well to claim Bosun Lawal’s cross, before Ryan Broom’s effort was deflected just wide as the first half ended goalless.
But O’s had a let-off within three minutes of the restart as Josh Vela fired wide with the goal at his mercy.
Aristote Nsiala picked up the first booking of the game for a foul on Graham, but James saw his free-kick saved by Lynch and Omar Beckles was shown a yellow card on 52 minutes.
Richie Wellens made a triple substitution and replaced Pigott, Moncur and captain Darren Pratley with Aaron Drinan, Ethan Galbraith and Jordan Brown, but Fleetwood broke the deadlock on 56 minutes as Jack Marriott found the net.
Beckles was then forced off with injury, to be replaced by Dan Happe on the hour, and Sotiriou fired wide from Drinan’s lay-off before Graham had penalty claims turned down.
Shaq Forde replaced El Mizouni in the fifth and final change for O’s to bolster their attacking options, with Junior Quitirna firing just wide for the home side on 69 minutes.
Johnston was booked for a foul on Sotiriou, but Promise Omochere escaped with a lecture after a challenge on Archibald.
And Brandon Cooper saw a far-post header cleared off the line on 81 minutes, before Sotiriou was shown a yellow card.
Archibald had a shot tipped over in the sixth minute of stoppage time, before Brynn denied Kabongo Tshimanga on a counter attack.
And Galbraith, booked alongside Brown moments earlier, was shown a second yellow card in quick succession for simulation and dismissed before the final whistle to compound O’s misery, as Johnston saw red for the hosts.
Leyton Orient: Brynn, James, Pigott (Drinan 53), Sotiriou, Archibald, Cooper, Moncur (Galbraith 53), El Mizouni (Forde 63), Pratley (Brown 53), Beckles (Happe 60), Graham. Unused subs: Howes, Hunt.
Attendance: 3,189.
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