Tries from winger Rhys Williams, who won the RBS Man of the Match award, and prop Adam Jones helped Wales build an 18-3 half-time lead and they underlined their superiority after the break with a second try from Williams.
Simon Taylor grabbed a last-gasp consolation try for Scotland, converted by skipper Chris Paterson, as Matt Williams' reign as coach began with a comprehensive defeat.
Wales went into the championship buoyed by an encouraging showing in the World Cup and a first victory in a championship opener since 1997 raises hopes that Steve Hansen's side can be a force to be reckoned with this year.
Wales got off to a flying start with a third minute try from right wing Williams.
Iestyn Harris made a half break and offloaded to full-back Gareth Thomas. He found support from flanker Martyn Williams and Rhys Williams surged over for the try. Stephen Jones' conversion gave Wales a 7-0 lead.
Paterson responded with a drop goal and, although Stephen Jones squandered a chance to re-establish a seven-point lead when he missed a straightforward penalty, Wales were soon celebrating a second try.
Swift handling stretched the Scottish defence before Stephen Jones, Thomas and Martyn Williams combined to create room for burly prop Adam Jones to cross near the left touchline.
Stephen Jones failed with the conversion but Wales led 12-3 and it was already looking ominous for the Scots.
A sweeping Wales counter featuring Duncan Jones, skipper Colin Charvis and Rhys Williams ended with Thomas surging over but Sonny Parker had inadvertently blocked off would-be Scottish tacklers and Irish referee Donal Courtney penalised the Welsh for crossing.
Stephen Jones softened the disappointment with his first penalty to give Wales a 15-3 lead.
A Simon Danielli break sparked a spell of Scottish pressure that brought no points and the right wing combined with skipper Chris Paterson to force replacement Wales prop Gethin Jenkins into touch when he threatened to claim a third try for the hosts.
Stephen Jones took Wales into the break with an 18-3 lead with his second penalty after Cameron Mather had been penalised at a maul.
Shane Williams was denied a try by Danielli's last-ditch tackle which meant he had a foot in touch before touching down one handed.
But Scotland's reprieve was shortlived. Gareth Cooper, Stephen Jones and Harris combined to create an opening and Rhys Williams, popping up on the left wing, cut inside the attempted tackle of Scottish replacement Dan Parks to claim his second try.
Stephen Jones' conversion hit the post but there was no way back for Scotland at 23-3.