Leyton Orient suffered their fifth league defeat in a row as two goals from Lee Miller gave Carlisle the win.
Orient, who remain without a point, scored when Dean Cox's cross was headed in from eight yards by Jimmy Smith.
But Miller, making his debut after joining from Middlesbrough, headed in from close-range after a right-wing cross from substitute Francois Zoko.
Miller grabbed the winner for Carlisle with a clinical finish after David Button had parried Liam Noble's shot.
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Leyton Orient manager Russell Slade told BBC London 94.9:
"Even though it was a tight game, I though for 60 minutes we were in control. We got the goal and I thought we deserved it.
"We were ok as soon as we scored the goal but for the last 25 minutes we didn't keep the ball well enough or have the authority we should have had when we went in front.
"They reacted quicker than we did and they punished us. They came looking for a point today and they've mugged us and gone home with three."