Ashley Johnson and Tom Varndell ensured a war of attrition burst to life, grabbing two tries in as many minutes as Wasps stung the reigning champions at Adams Park.
A nip-and-tuck battle saw the sides head into the break level at 3-3, before two Stephen Myler penalties after half-time edged Northampton Saints ahead.
However, Wasps pounced on the hour mark, Johnson first grabbing an intercepted try before Varndell’s chip-and-chase put them more than a score ahead – with the help of two superb Ruaridh Jackson conversions.
Ben Foden’s late try kept the tie alive but Wasps held on not only to bounce back from last-gasp defeat at last weekend’s London Double Header, but also from a 74-13 thrashing the last time these two sides met.
A couple of early penalties in the Wasps 22 allowed Northampton to signal their intent, Myler kicking for the corner twice in quick succession, but the hosts were unmoved in defence.
Andy Goode was twice offered the chance to clear before a stolen lineout ensured the pressure was soon back on but this time a pair of big hits from Chris Bell in midfield stopped the visitors in their tracks.
Myler was first to draw blood, on 11 minutes, with a straightforward penalty after Northampton got the better of their hosts at scrum-time.
However, the Saints were soon caught off their feet at the breakdown twice in quick succession and on the second occasion Goode pointed to the posts and restored parity.
Northampton’s ill-discipline at the breakdown continued to undo much of their good work and ten minutes after his first penalty Goode was handed another, only to send it wide of the left-hand post from 43 metres.
With half-time approaching, Varndell got the Adams Park crowd on its feet with a powerful break down the left flank but turnover ball got the Saints out of jail inside their own 22.
Goode sent an early drop-goal attempt wide after the break, while Myler responded by grazing the outside of the right-hand post with a penalty.
Saints thought they had carved out the opening try when George North got on the end of a Ken Pisi chip but the winger was ruled offside – though referee Luke Pearce did bring back play for an earlier penalty and Myler made it 6-3.
Replacement scrum-half Kahn Fotuali’i added some life to the Northampton attack, prompting a powerful rolling maul which resulted in another penalty and three more points for Myler.
But, not long after that six-point lead had opened up it was Wasps who finally ended the wait for a try on the hour mark, through flanker Johnson.
Some smart offloading saw the Saints spread it wide but when Luther Burrell looked to the wing Johnson was one step ahead, intercepting and haring clear of Myler, who was in pursuit.
Jackson added an excellent conversion from the right touchline to put Wasps ahead and they were further in front just two minutes later.
Varndell collected the on the left touchline and touched down after a pinpoint chip-and-chase, with Jackson making it two from two off the tee.
Jackson was forced off injured, leaving Rob Miller in charge of kicking duties but he hit the ground running, slotting is first penalty to make it 20-9.
Foden crossed over to put the pressure on in the final two minutes and Myler converted to move them within six points but the task proved too much for Jim Mallinder’s men.