The result keeps the Cumbrians on course for a second successive promotion, while defeat for Darlington leaves their play-off hopes in big doubt.
Captain Kevin Gray opened the scoring, before second half goals from Derek Holmes, Michael Bridges, Glenn Murray and Simon Grand inflicted the Quakers' to their heaviest loss of the season.
Just moments after Simon Johnson struck the Carlisle post Gray broke the deadlock on the stroke of half time. After some hesitant home defending, Danny Livesey hooked the ball up to Gray who nodded past Sam Russell.
Worse was to follow for the Quakers keeper after the break. After failing to control Matthew Clarke's back pass, Holmes pounced to make it 2-0.
Former Sunderland man Bridges added a third with a superb finish across the face of Russell. It could have been four soon after when Gray hit the post from an acute angle.
Cumbrians' keeper Keiren Westwood produced a superb save to tip Neil Wainwright's curling effort around the post, while at the other end, Karl Hawley came within inches of adding to the tally when he flashed a shot narrowly wide.
Sub Murray made it four in the 88th minute when his speculative effort squirmed off the body of Russell.
The Quakers keeper completed a miserable afternoon when he was lobbed by Grand in stoppage time.