The game, at Millennium Stadium, got off to a dream start for Declan Kidney's men.
Tries by Simon Zebo - making his first 6 Nations appearance - and Cian Healy, plus 10 points from Jonathan Sexton, ensured that Ireland dominated their hosts during the opening half-hour.
The stunned Grand Slam champions found themselves facing an eighth successive loss.
And any faint hopes that they would stage a fightback seemed to be obliterated just two minutes after half time, when the influential centre Brian O'Driscoll dived over from two feet out.
O'Driscoll, Rob Kearney, Rory Best and Sean O'Brien were all restored to Ireland's starting XV after missing the autumn schedule through injury - although Jamie Heaslip replaced O'Driscoll as captain.
Despite Ireland racing into a 30 points to 3 lead, Wales did fight back in the end though and saw tries scored by Alex Cuthbert, Leigh Halfpenny and Craig Mitchell.
But it was case of too little, too late.
The final 22-30 score leaves Wales' interim head coach Rob Howley still searching for a first win against another Test-playing country, as they prepare to meet title favourites France.
After the match coach Declan Kidney said he hoped O'Driscoll would grace this tournament for at least another year.
With Brian it is just a privilege to be working with him.
Ireland coach Declan Kidney
He said: "Brian will make up his own mind. I would not like to sway him one way over the other.
"The bottom line is you would love to have the guy around forever wouldn't you?
"But if you look at the performance he put in today, that is not easy on the body.
"Huge credit to him, given the amount of game time he has had, to come out and give such an international class performance like he did today.
"It is wrong to say it doesn't surprise you, as normally you should not be able to pull out a performance like that with the amount of game time he has under his belt.
Ireland are facing France and England on home soil this year, but Kidney isn't willing to talk about their Grand Slam chances.
He said: "I don't buy into that because it means we should not bother every other year as we have no chance.
"If you look at the second half here, we still have a lot of work to do.
"England and France are playing well and we still have to go to Murrayfield where we lost the last time we were up there."