Ireland were as clinical as they come in the first 40 as they claimed two converted tries from Simon Zebo and Cian Healy, together with three penalties from Jonny Sexton. Man of the match Brian O'Driscoll crossed for a third Irish try just moments after the break but Wales hit back with three tries of their own through Alex Cuthbert, Leigh Halfpenny and Craig Mitchell.
It was too little, too late for the holders, though, as Ireland held on to inflict a fifth straight home defeat on the Welsh, who have now lost eight games in a row since the Grand Slam win over France 11 months ago.
Former Lions skipper O'Driscoll did his hopes of a fourth tour the power of good as showed he still has what it takes at the highest level with a stunning individual performance. The 34-year-old centre produced a superb piece of individual skill to set Ireland on their way as Wales failed to fire early on at the Millennium Stadium. O'Driscoll drifted outside Jonathan Davies 20 metres out before committing Halfpenny and passing behind Cuthbert's back in one seemingly fluid motion. Zebo was left with a simple run in for his second international try as Ireland ended a 10-minute stalemate.
Sexton's conversion was followed by a 21st-minute penalty before Healy pushed them further in front just over two minutes later. Rory Best's chargedown of Dan Biggar's attempted clearance was the initial catalyst, with Best's long pass finding Jamie Heaslip, who shipped it on to Zebo.
Heaslip's pass could easily have gone to ground but Zebo somehow flicked it up into his hands with his heel to keep the move alive, with Healy barging his way over for Ireland's second score.
Sexton's second conversion and second penalty had Ireland 20 points to the good before Halfpenny finally got Wales on the board after 33 minutes. A third penalty from the impressive Irish playmaker then made it 23-3 on the stroke of half-time and left Wales with a mountain to climb in the second period.
Their Everest got even taller and tougher when O'Driscoll snuck home from a ruck just shy of the Welsh line after 43 minutes as Ireland moved 30-3 in front courtesy of another successful conversion from Sexton.
That really should have been that as far as Ireland were concerned but Wales refused to give up the ghost and were soon celebrating their first try as Cuthbert sliced through from 10 metres out with 48 minutes gone. Patience paid off for the hosts as they hammered away in the Irish 22 before the giant Blues wing left 2009 Lion Keith Earls clutching at thin air after he picked a perfect line off Biggar.
Halfpenny's conversion gave Wales hope and that hope was increased when Best's 57th-minute yellow card was followed by a second welsh try just two minutes later. Simple hands from Jonathan Davies and Jamie Roberts put Halfpenny in at the corner, with the TMO confirming that Zebo and Sexton hadn't done enough to force him into touch.
The difficult extras didn't hit the target but the Welsh comeback was given even greater emphasis when Connor Murray was sent to the sin bin on 70 minutes after the Irish defence had held firm under substantial pressure.
Murray's absence led to replacement prop Mitchell's converted close-range try six minutes later but that was as close as Wales got to a miracle recovery. Ireland ran down the clock in the closing stages to record a deserved victory that comes on the back of a brilliant showing against Argentina last time out.
Next up for Ireland is a home tie with England on Sunday, February 10, while Wales face three successive away games, starting against the French in Paris on Saturday.