First-half strikes from Tom Shanklin and Alun-Wyn Jones set the 2008 Grand Slam winners on their way at Murrayfield.
Wings Leigh Halfpenny and Shane Williams added further tries after the break to seal the victory for Warren Gatland's men.
The Dragons had been rocked with an injury blow before kick-off when skipper Ryan Jones failed a late fitness test with a calf strain to join Gavin Henson, who pulled out earlier in the week, on the sidelines.
That opened the door for Dafydd Jones to start at blindside flanker with double Lions tourist Martyn Williams taking over the armband on his 85th cap.
Wales flew out of the traps and were denied the opening try in the tenth minute following a huge tackle by Scottish wing Simon Webster on veteran flanker Williams.
But the visitors' sustained pressure eventually told two minutes later when fly-half Stephen Jones booted home a close-range penalty.
Scotland saw debutant Geoff Cross - who fought back the tears during the anthems - stretchered off with a nasty head injury after a sickening mid-air clash with Lee Byrne. Cross' misery was compounded when Irish referee Alain Rolland banished the yellow card for a dangerous tackle as the Edinburgh prop way to the dressing room.
And, within a minute, Wales capitalised on the extra space as Shanklin touched down for his 19th Test try following neat work by Shane Williams and Byrne.
Wales showed their ruthless streak and hammered home their advantage when second-row Jones fended off Hugo Southwell's tackle for the second try on 28 minutes.
Replacement Chris Paterson slotted home a 35-metre penalty before the rampaging Andy Powell, on his first Six Nations start, denied Scotland's record points scorer a certain try with a superb covering tackle.
Wales were in command and extended their 16-3 interval lead when Halfpenny borrowed over in the 41st minute from Shane Williams' pass before the wing wizard got in on the act with the fourth try on the hour mark.
With skipper Martyn Williams in the sin-bin, Wales endured a nervy final quarter as Max Evans slipped Shane Williams' tackle for his first try for Scotland with the Ospreys star worryingly limping from the field with an ankle injury.
Scorers
Scotland: Try: M Evans; Pens: Paterson (2); Con: Paterson
Wales: Tries: Shanklin, AW Jones, Halfpenny, S Williams; Pens: S Jones (2)
