Preston best Carlisle 3-1 on penalties after the sides had fought out a 1-1 draw in normal time in the Johnstone's Paint Trophy first-round tie at Brunton Park.
David Buchanan fired home the decisive spot-kick after the home side had missed three times in succession.
Chris Beardsley had given Preston a third-minute lead which was cancelled out in the second half by Jon-Paul McGovern to send the tie to penalties.
Carlisle brought in keeper Mark Gillespie for his home debut and his first action was to pick the ball out of the net as Beardsley opened the scoring for North End, deflecting David Amoo's driven cross form six yards giving the youngster no chance.
Beardsley, having scored his first goal since joining Preston from manager Graham Westley's former club Stevenage, could have snatched a second but for an offside decision after Amoo had sprinted 50 yards deep into Carlisle territory before picking out the striker with his cross.
There was a massive improvement in Carlisle's performance in the second half and Matty Robson was denied right on the line by keeper Steve Simonsen's diving save from a point-blank header.
McGovern fired Carlisle level in the 68th minute when the ball was played square to him across the edge of the penalty area and he hammered an 18-yard shot right-footed to the keeper's left and just inside the post.
Carlisle were reduced to 10 men when, with seven minutes to play, Liam Noble was shown a straight red card for a studs-showing tackle on Nicky Wroe.
In the dying seconds, Preston almost benefited from the extra man as substitute Akpo Sodje hit the woodwork with a first-time strike.