Lee Miller struck twice to hand Carlisle a 2-1 victory at Leyton Orient.
It was the home side who enjoyed the greater possession in the opening 45 minutes, with midfielder Dean Cox twice seeing efforts deflected for corners and David Mooney only denied by a last-ditch tackle from defender Stephen O'Halloran.
Orient went in front after 53 minutes when Cox floated a free-kick into the box and midfielder Jimmy Smith stole in to head the ball past Adam Collin from eight yards.
Yet the visitors levelled 15 minutes later when substitute Francois Zoko raided down the right side and delivered a pinpoint cross to the far post where the unmarked Miller, a midweek signing from Middlesbrough, was left with a simple close-range header.
And with just three minutes of normal time remaining, Carlisle won a free-kick and debutant goalkeeper David Button tipped a 35-yard free-kick onto the crossbar.
The ball fell to Liam Noble whose shot was also parried by Button before Miller applied the clinical finish to leave Orient rock-bottom of the league and still seeking their first point of the season.
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