Leicester Tigers' perfect record in the Premiership this season was ended by Wasps, who kept the leaders scoreless in a much-improved second-half display.
Tigers, who had won 11 games on the spin, led 13-7 after Julian Montoya's try and two George Ford penalties despite conceding an early penalty try.
However, Wasps showed much more adventure after the break and Jimmy Gopperth's boot edged them ahead.
With time ticking down, Tigers mounted a late surge, but the hosts stood firm.
Steve Borthwick's Tigers turned up at the CBS Arena knowing a win would merit a 16th in all competitions this season, equalling a club record set in 1983-84.
Their opening 40 minutes suggested they would have no issues in matching that feat, despite the sin-binnings of Tommy Reffell and skipper Ellis Genge - the former for the off-the-ball tackle which brought Wasps a penalty try and the latter for a strike to the face of Francois Hougaard.
Wasps barely got out of their own half in that period as stand-off Ford kicked the visitors about smartly, although the England international's two misses from the tee would eventually prove costly.
Wasps head coach Lee Blackett knew a second-half improvement was necessary and a tactical switch provided it.
Gopperth's work at inside centre complemented the halves work of Sam Wolstenholme and Charlie Atkinson as Wasps took the ball to the line and forced Tigers back.
Former Junior All Black Gopperth's boot did enough to whittle away the deficit and, once the lead had been taken, Wasps survived numerous scrum resets and a pounding of their line to squeeze out a huge victory - a perfect tonic to their New Year's Day slump at Sale.
Wasps head coach Lee Blackett told BBC CWR:
"It wasn't perfect, far from it, but after the game it was emotional. It was pretty hard to speak. You don't get carried away but we're in the game to celebrate big wins like this.
"It was built on a lot of emotion and a lot of energy, it was gritty, you had to scrap and fight and I thought our young half-backs, the way they managed the game - which you have to do against Leicester - did really well.
"Probably it was the built up emotion of the last five minutes, when you go to the scrum and you've got young Zac [Nearchou] coming in. We know what happened against Harlequins, I think he's worked so hard on his game and it was great to see. That's when you see young guys come of age."
Leicester director of rugby Steve Borthwick told BBC Radio Leicester:
"The players' effort was excellent, they tried tremendously hard, but we made too many mistakes. That cost us. Wasps played really well, they deservedly won the game.
"That third quarter of the game, we lost the penalty count and they played really well, powerfully, and from a position where we could have won the game, we went behind on the scoreboard.
"It doesn't matter what the result has been in any situation, there's always a job as a coach and a group of people. We'll look at what we could have done better and become a better team.
"It wasn't long ago that Leicester came into a game hoping to win and now we're disappointed we've lost. We've got plenty to prove but it shows we've made some change."
Wasps: Crossdale; Hougaard, Spink, Gopperth, Bassett; Atkinson, Wolstenholme; Hislop, Cruse, Toomaga-Allen, Cardall, Stooke, Barbeary, Shields (capt), Willis.
Replacements: Frost, Nearchou, Alo, Gaskell, Young, W Porter, Mills, Miller.
Leicester: Steward; Potter, Scott, Kelly, G Porter; Ford, Van Poortvliet; Genge (capt), Montoya, Cole, Green, Snyman, Wells, Reffell, Chessum.
Replacements: Clare, Whitcombe, Heyes, Murimurivalu, Dolly, B Youngs, Burns, Moroni.
Sin-bin: Reffell (3 mins), Genge (40 mins).
Referee: Tom Foley (RFU).