Kazeem Olaigbe had fired Town into a third minute lead, though David Norman and Sam Hoskins both found the net to turn the tie around by the half hour mark.
With seconds to go until the break, Kieron Bowie was able to guide the ball into the top corner with a first time volleyed finish, that made it too big of a deficit for Town to recover from on this occasion.
Simon Weaver named the same squad that swept aside Walsall on Tuesday night, while hosts Northampton made just the one change as Max Dyche returned from injury.
It took just three minutes for Town to take the lead with Olaigbe providing another fine finish, finding the bottom left corner after Luke Armstrong had chased down a long Mark Oxley pass and managed to divert the ball in Olaigbe’s direction via a deflection.
Northampton would equalise in the 10th minute though, Norman getting his head to an inswinging corner and seeing his attempt cross the line after bouncing back off the far post.
Harrogate responded well to conceding the equaliser with Matty Foulds going close to his first Town goal, heading Josh Falkingham’s deep cross into the arms of Lee Burge.
The hosts found themselves ahead in the 23rd minute though through top scorer Hoskins, who had carried the ball forward from right wing back before playing a one-two and firing across Oxley.
Weaver’s side again responded well to conceding as Olaigbe saw his shot deflected, before Warren Burrell who had replaced the injured Alex Pattison, suffered the same fate with his well struck attempt.
Deep into stoppage time Northampton grabbed a third goal when Mitch Pinnock stole possession from Matty Foulds and found Bowie, who guided the ball first time into the top corner to put the hosts in a commanding position at the half way point.
The Cobblers made a good start to the second half with Mitch Pinnock going close to adding a fourth and securing the points, his first effort beaten away by Oxley before dragging wide from just outside the area.
Town responded with some attacks of their own, Olaigbe again having a go from range before Weaver opted to introduce Matty Daly into the mix, in place of George Thomson.
Jack Muldoon was also introduced from the bench and went close to pulling a goal back in stoppage time, though Town couldn’t find a second goal that would have forced a grandstand finish as Town suffered a first defeat in seven.
Town: Oxley, Falkingham, Thomson (Daly 65), Olaigbe, Folarin (Muldoon 77), Sims, O’Connor, Pattison (Burrell 28), Armstrong, Foulds, Eastman.
Subs not used: Jameson, Mattock, Angus, McArdle
Goals: Olaigbe 3
Northampton: Burge, Sherring, Hoskins (Eppiah 90+), Appere (Yengi 90+), Pinnock, Leonard, Norman (McWilliams 45), Hondermarck, Bowie (Hylton 80), Haynes, Dyche
Subs not used: Wright-Phillips, Osew, King
Goals: Norman 10, Hoskins 23, Bowie 45+2
Booked: Hondermarck
Referee: Seb Stocksbridge
Attendance: 7,018 (107 away)