A first career hat-trick for Leon Clarke secured a third successive victory for Chesterfield.
The striker, on loan from Swindon, struck early from close range after good work by Craig Westcarr but Lee Miller equalised with a firm volley.
Clarke's glancing header restored the hosts' advantage and he bundled the ball home for his hat-trick after Carlisle failed to clear a free-kick.
Westcarr completed the scoring when he headed home Nathan Smith's chip.
VIEWS FROM THE DRESSING ROOM
Chesterfield manager John Sheridan told BBC Radio Sheffield:
"It was a very difficult game, they're a very good team.
"It think our game today was very good from one to 11, and I thought as a team we played really well, lots of energy.
"I thought that the football played today was very good from both sides. I thought we deserved to win the game, Carlisle are a good side and they've done really well over the years in this division so I thought we performed very well."
Carlisle United boss Greg Abbott told BBC Radio Cumbria:
"I don't like criticising the players in public, and at the end of the day I will take full responsibility.
"The players have said that once they have crossed the white line it is up to them, they have got to stop making mistakes and stop giving the ball away, and if they do they are the ones that have got to defend the goal better.
"They are a really good set of players, and I need them probably to be not as such a good group of players, to be a team of brutes with a nastiness and an edge to them.
"Do we sacrifice passing and attacking play to make us more resolute? The fans at Brunton Park have been chasing attacking football for a long time, but I am sure they would rather see us win in some shape or form than play open football and get beat."