Only two minutes had been played when Theo Archibald’s deflected free-kick gave Tomas Holy some concern.
And Holy managed to gather a cross from Idris El Mizouni as Shaq Forde lurked moments later.
Sol Brynn was called upon to make a fine save a header from Jon Mellish on eight minutes, before Dan Happe was caught high in the visiting box and O’s were awarded a penalty.
Joe Pigott stepped up to convert calmly from the spot, with Carlisle forced into a change soon after when Callum Guy was stretchered off to be replaced by Dylan McGeouch.
Holy got to a lovely cross from Tom James just before Forde on 26 minutes, then cut out a cross from Archibald soon after as O’s continued to enjoy some good possession.
Sean Maguire sent an overhead kick just over Brynn’s crossbar on 34 minutes, but the tempo then slowed somewhat as O’s remained continued to look comfortable.
Forde was close to getting on the end of Pigott’s flick as the first half drew to a close, with Pigott having an effort ruled out during stoppage time when the linesman ruled the ball had gone out of play.
Aaron Drinan replaced Forde during the break, but Brynn had to make a fantastic save to deny Joe Garner four minutes after the restart.
However, the respite was brief for O’s as Garner levelled moments later, with James sending a speculative effort drifting wide of the target as the hosts sought to respond.
Drinan’s cross was deflected behind on the hour, but Idris El Mizouni was then booked for a trip on Jordan Gibson as Carlisle broke upfield.
O’s regained the lead on 64 minutes, though, when Drinan met a left-footed cross from James and squeezed the ball in at the far post.
And Drinan went close to making it 3-1 six minutes later as he met a cross from Archibald, but Holy’s magnificent save denied him.
Happe was next to have his name taken, before Robinson was booked for a late challenge on Ethan Galbraith.
And O’s were inches away from a third when the ball bounced off Corey Whelan and hit the crossbar with Holy stranded.
Pigott had penalty claims turned down with a quarter of an hour remaining, with Archibald firing into the side netting from outside of the box.
And Richie Wellens made a double change in the final quarter of an hour as George Moncur and Ruel Sotiriou replaced Galbraith and Pigott.
Sotiriou sealed victory in the last minute of normal time after being played in on the right, as he fired through the legs of Holy for his sixth of the season.
And the substitute might have added further gloss in stoppage time, but fired wide after a quick break.
Leyton Orient: Brynn, James, Turns, Happe, Brown, Pigott (Sotiriou 76), Archibald, Cooper (Sweeney 63), El Mizouni (Pratley 90), Forde (Drinan 46), Galbraith (Moncur 76). Unused subs: Howes, Beckles, Pegrum.
Attendance: 3,808 (including 463 Carlisle fans).
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