Tranmere conceded an early goal before hitting four past Northampton.
Ryan Gilligan capitalised on a poor backpass from Ian Goodison to put the visitors in front, but striker Bas Savage levelled with a clinical finish.
Antony Kay put the home side in front three minutes later before Craig Curran added a third in a goalmouth scramble after Kay had headed onto the crossbar.
In the second half, substitute Chris Greenacre set up Ian Moore, who tapped in to heap more misery on Northampton.
Tranmere Rovers manager Ronnie Moore told BBC Radio Merseyside:
"I thought we were the best side by a mile, we gave them a goal which they didn't have to work for, but even then there was no panic on.
"I think we've been brilliant today, the passing, the movement, the pace upfront, the work ethic all over the park - I couldn't fault it.
"I thought [Bas Savage] was brilliant, that's the standards you set and you have to produce them every week."
Tranmere: Coyne, Edds, Chorley, Goodison, Taylor, Shuker (Moore 71), Kay, Jennings, Sonko, Curran (Greenacre 88), Savage. Subs Not Used: Achterberg, O'Callaghan, Shotton.
Goals: Savage 35, Kay 38, Curran 45, Moore 90.
Northampton: Dunn, Little, Hughes, Doig (Dolman 46), Jackman, Osman, Crowe (Davis 70), Coke, Holt, Akinfenwa, Gilligan (Henderson 36). Subs Not Used: Walker, Dyer.
Goals: Gilligan 10.
Att: 5,034
Ref: Mark Haywood (W Yorkshire).
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