Wasps secured both the English and European crowns at HQ last season, but a committed display from Saracens saw the double champions succumb to a late-gasp penalty from Fiji fly-half Nicky Little.
It was a disappointing way for England star Matt Dawson to start his Wasps career, and the scrum-half was forced to watch as Kyran Bracken – his long-time rival for the England No.9 jersey – split the Wasps defence to set up Saracens' only try in the 25th minute.
Bracken's jinking run ended when he was hauled down just short of the line, but prop Kevin Yates exploited the gap to go over in the corner.
Thomas Castaignède added the conversion, and last season's underachievers went into the break with an improbable 10-3 lead.
Wasps unleashed their England contingent onto the Twickenham turf for the final 40 minutes of the game, and fly-half Alex King began to get the black and yellow backline purring.
King and hooker Ben Gotting combined in a one-two passing move to open up the Saracens' defence, and duly sent centre Ayoola Erinle over for an unconverted try to cut the deficit to 10-8 in the 49th minute.
King then took over the kicking from Mark van Gisbergen and landed a penalty which edged them 11-10 in front.
But King missed a second attempt just minutes later that could have sealed matters.
Little then missed two penalty attempts himself, before steadying his nerve to slot over the killer with just three minutes left on the clock.
Wasps threw everything at their London rivals in a last-ditch assault, but the Saracens' defence held out.
Wasps have now only won one opening day fixture in the last seven season.
For Saracens:Try: Yates Cons: Castaignède Pens: Castaignède, Little
For London Wasps:Tries: Erinle Pens: King, Gisbergen