David Ball and Antoni Sarcevic struck early in each half as the Cod Army advanced to the Northern Area semi-finals at the expense of the two-time winners of the competition.
Ball got the hosts off to a flying start with a goal after five minutes. His initial shot was saved by Carlisle goalkeeper Greg Fleming but the rebound fell nicely to Sarcevic who ran to the byline and cut the ball back for Ball to net from close range.
The Cumbrians were poor but should have equalised when space opened up for Brad Potts to sneak into the box, but his shot struck the inside of a post.
Fleetwood controlled the first half, with Sarcevic and Jeff Hughes both wasting good chances to extend the lead.
Carlisle threw Lewis Guy into the action at the break but they could not hold back the League Two side and Sarcevic doubled the advantage in the 54th minutes, lobbing Fleming after a long ball forward from Gareth Evans.
Sarcevic nearly added a third when his shot flashed across the face of goal after good work from Evans down the left.
Substitute Junior Brown also went close to making it 3-0 but was denied by his team-mate Jon Parkin who got in the way of his goal-bound effort.