Town progressed to the quarter-finals of the Carling Cup for the first time in nine years.
Blues had to come from behind to do it though, Liam Davis giving the Cobblers the lead on 16 minutes with a 25 yard strike.
Carlos Edwards equalised for Town soon after with a terrific right foot finish and Damien Delaney put Blues in front just before the break with his first goal for the Club and his first in 18 months.
Tamas Priskin sealed the win with a looping header from Grant Leadbitter's free-kick two minutes from time.
Roy Keane made three changes to the side that went down at Forest on Saturday, Brian Murphy returning in goal with Tom Eastman and Priskin included in the starting line-up.
Priskin tested Chris Dunn in the Northampton goal with a 25 yarder from the angle, while at the other end Billy McKay let fly at the Town goal, Murphy equal to the task.
Dunn was quick off his line to clear from Priskin outside his box, then Edwards' touch let him down when the Trinidad international had an opening after good work by Jason Scotland.
The Cobblers' travelling army were on their feet on the quarter hour, Davis spun away from his marker and beat Murphy from 25 yards to find the top of the net.
Edwards responded with a shot that deflected wide off Gareth McAuley but on 26 minutes, the former Sunderland player levelled the scores, taking advantage of a slip by Davis and firing superbly past Dunn into the far corner.
Scotland and Priskin linked up to test Dunn again, the Northampton 'keeper then denying Grant Leadbitter from 20 yards and David Norris from the follow-up.
The Cobblers' No.1 was beaten just before the break though, Delaney thundering in a left foot rocket from just inside the box to give Blues the advantage at the break.
Delaney was in the thick of the action inside the first minute of the second-half, his run and pass finding Scotland, the striker releasing Priskin whose shot was deflected wide for a corner.
Dunn beat Priskin after the Hungarian raced on to Tommy Smith's header, Andros Townsend's dangerous cross beating everyone as Town pressed for a decisive third goal.
Townsend let fly at Dunn from the edge of the box, the 'keeper holding firm. Michael Jacobs then firing over at the other end after Grant Leadbitter had given away possession.
Priskin was denied again by Dunn after Scotland's shot had fallen into his path before Blues made a double change on 68 minutes, Jaime Peters on for Townsend and Ronan Murray for Scotland. Northampton replacing Kevin Thornton for Andy Holt.
Murray didn't get enough on the ball with a curling effort that went straight at Dunn. Murphy then doing well at the other end to take a cross from Ryan Gilligan inside his six yard box.
McAuley had a header pushed behind by Dunn, the Town defender then having an anxious second as a long throw bounced off his chest into the air, Murphy ending the danger.
Priskin made sure of Blues' passage to the last eight with a header from Leadbitter's free-kick as the clock ticked around to 90 minutes.
There was just time for Jamie Griffiths to make his debut for Blues, coming on for Edwards in added on time as Town can look forward to being in the hat for the quarter-final draw on Saturday.
Town: Murphy, Eastman, McAuley, Delaney, Smith, Edwards (Griffiths 90), Leadbitter, Norris, Townsend (Peters 68), Scotland (Murray 68), Priskin. Subs not used: Fulop, O'Connor, Hyam, Brown.
Northampton: Dunn, Rodgers, Hinton, Hall, Davis, Gilligan, Osman, Wedderburn, Jacobs, Thornton (Holt 69), McKay. Subs not used: Walker, Guinan, Konstantinou, Harris, Slowe, Kaziboni.
Att: 12, 929