High-flyers Orient had launched a series of attacks in the opening half and had been thwarted by three outstanding saves by Carlisle goalkeeper Greg Fleming on his league debut.
The Cumbrians goalkeeper twice clawed away goal-bound efforts from Kevin Lisbie and also produced an excellent save to deny Robbie Simpson.
But Fleming was finally beaten after 44 minutes when Scott Cuthbert rose high to power home Lloyd James' corner from eight yards to give the O's a deserved lead.
Fleming was beaten again two minutes into the second half following another James' corner.
The midfielder's right-footed set-piece was partially cleared and substitute Jamie Ness, on loan from Stoke, struck a wonderful left-footed volley into the net from 25 yards to record a goal on his home debut.
Totally dominant, the O's made it 3-0 after 66 minutes when Lisbie unleashed a powerful 18-yard drive that went in off the post to record his 11th league goal of the season.
It ended a personal drought for the striker who scored for the first time since October 26.
Then deep into time added on Spurs loanee Shaq Coulthirst capitalised on an error by the visitors' defence to stroke the ball home from close range.