Saints suffered their fourth successive defeat as Wasps again stung Jim Mallinder's men at Franklin's Gardens.
The Coventry-based club had won on their previous two visits to Northampton, and they earned an impressive bonus-point 38-22 victory on this occasion.
Saints were in the game at half-time at 16-11 down, but a yellow card for Ben Foden and some porous defending ruined any chance of victory.
Wasps scored four tries on the day, through Christian Wade, Ashley Johnson, Josh Bassett and Juan de Jongh, as they earned their fifth successive win against Mallinder's men.
Piers Francis, who was forced off with an injury during the second half, kicked well for Saints, registering 12 points, while Ahsee Tuala finished off a tidy try, created by Foden.
Harry Mallinder also added an eye-catching late effort.
But it wasn't to be enough as Wasps cruised to victory, securing only their third win in seven Aviva Premiership games this season.
Saints have now lost three of their seven and will return to league action at Worcester Warriors on November 18 aiming to bounce back from back-to-back Premiership defeats.
The green, black and gold had emerged with real purpose despite coming into this game after two Champions Cup losses, putting early pressure on Wasps.
But the away side were looking typically dangerous on the counter-attack and they sprung from their own half to set up an early chance to register some points.
The Wasps pack turned on the power at the scrum and referee Luke Pearce awarded a penalty, which Jimmy Gopperth landed to give his team the lead.
But Saints levelled it up almost immediately, with fly-half Francis placing a penalty of his own between the posts.
Gopperth quickly put Wasps back in front after Tom Wood was penalised, but a piece of brilliance was to help Saints to regain their lead.
Foden gathered a clearance kick, sold his man a dummy and sent Tuala away, with the full-back having the simple task of dotting down in the corner.
Francis missed the conversion to leave the score at 8-6 and Wasps were back in front for a third time when Gopperth added another penalty to the tally.
It was an ebb and flow game, with both sides looking dangerous when springing from their own half.
And Wasps turned defence into attack in seconds to score their first try as hooker Johnson's clearance was chased down by the speedy wing Wade, who also converted.
Francis narrowed the gap to five points with a penalty soon after, but Saints were reduced to 14 men before the break as Foden was sin-binned for a deliberate knock-on.
Wasps thought they had scored when scrum-half Dan Robson dotted down, but his foot was deemed to be in touch, even though the replays suggested otherwise.
Saints then stood tall after another penalty was kicked to the corner, turning the ball over and holding out to ensure they would remain 16-11 down at the break.
But Wasps didn't have to wait long to make the most of their numerical advantage count in the second half as Johnson found space to finish a flowing move.
Gopperth spurned the conversion chance, but his side had a healthy 21-11 lead.
Foden returned to the field to boost the home ranks, but they were still finding it tough to break down the white wall.
Francis did get the chance to narrow the gap with a penalty, which he struck sweetly to register a timely three points with 25 minutes to go.
And Francis slotted an even better effort two minutes later as he notched a penalty from just inside the Wasps half, bringing an expectant roar from the home fans.
Saints were now just four points down and they appeared to have the momentum, but Wasps soon put another spanner in the works.
Wing Bassett skipped inside and beat Tuala to score, with Gopperth's successful conversion putting Wasps back in a position of real command.
And their grip on the game got even tighter after a high tackle on prop Jake Cooper-Woolley gave Gopperth another three points.
Saints were continually being put under pressure and Wasps grabbed the bonus-point try they craved as centre de Jongh flew through the middle and scored.
Gopperth again converted as the away supporters celebrated a fine afternoon, but it was getting worse for Saints as Francis had to be helped from the field.
There was to be one late consolation score for Saints as Harry Mallinder, on for Tuala, sped down the left and scored.
Mallinder missed the rushed conversion and that was to be that as the home supporters flooded out of Franklin's Gardens after a hugely disappointing day for their team.
Saints: Tuala (Mallinder 63); Foden (Pisi 61), Tuitavake, Burrell, Collins; Francis, Groom (Reinach 63); Waller (Van Wyk 66), Hartley (c) (Haywood 75), Brookes (Hill 61); Lawes, Ratuniyarawa (Paterson 57); Gibson (Day 66), Wood, Harrison.
Wasps: Le Roux; Wade, Daly (Miller 40), De Jongh, Bassett; Gopperth, Robson (Simpson 63); Mullan (McIntyre 53), Johnson, Cooper-Woolley; Launchbury (c), Rowlands (Gaskell 57); Haskell, Young, Thompson.
Referee: Luke Pearce