This was the first Irish win on Welsh soil since 2005 and Gillian Bourke's late try proved decisive in the 12-10 cliff-hanger at Aberavon RFC's grounds in Port Talbot.
It was a tenacious fight-back from Philip Doyle's side who suffered a sin-binning in each half with forwards Sophie Spence and Stacey-Lea Kennedy seeing yellow.
From a five metre scrum second row Spence did extremely well to ground the ball in the left corner for the game's opening try after 22 minutes. UL Boh's Niamh Briggs added a brilliant conversion from the touchline.
The sides were level going in at the break after a 38 minute try from fullback Rosie Fletcher was converted by Elinor Snowsill.
The home-side pushed ahead with a Laura Prosser penalty with 11 minutes remaining but Ireland fought back showing great determination, and following a number of attacking phases the match-winning score came from Gillian Bourke, who had notched three tries in her last two outings against Wales.
Briggs was unable to add the conversion, but it was not needed as the girls in green made a winning start to the Six Nations, joining Italy and table toppers England on two points after the first weekend's action.
Next up for Ireland Women is England on Saturday at Ashbourne RFC, ko 2pm.
Ireland Women: Niamh Briggs (UL Bohemians/Munster); Niamh Kavanagh (UL Bohemians/Munster), Grace Davitt (Cooke/Ulster), Jenny Murphy (Old Belvedere/Leinster), Alison Miller (Portlaoise/Connacht); Lynne Cantwell (Richmond/Exiles), Larissa Muldoon (UWIC/Exiles); Fiona Coghlan (UL Bohemians/Leinster) (capt), Gillian Bourke (UL Bohemians/Munster), Ailis Egan (Old Belvedere/Leinster), Sophie Spence (Mowden Park Sharks/Exiles), Marie Louise Reilly (Old Belvedere/Leinster), Laura Guest (Highfield/Munster), Claire Molloy (Bristol/Exiles), Joy Neville (UL Bohemians/Munster). Replacements: Stacey-Lea Kennedy (City of Derry/Ulster), Fiona Hayes (UL Bohemians/Munster), Lauren Day (Waterloo/Exiles), Heather O'Brien (Highfield/Munster), Siobhan Fleming (Tralee/Munster), Amy Davis (Blackrock College/Ulster), Nora Stapleton (Old Belvedere/Leinster), Ashleigh Baxter (Belfast Harlequins/Ulster).
Ireland U20s suffered a 17-15 loss to Wales in their opening game of the U20s RBS 6 Nations on Friday night at Colwyn Bay.
Mike Ruddock's youngsters, who had 13 Championship debutants in their starting line-up, led 7-3 at half-time thanks to a try by man of the match Luke McGrath, converted by Tom Daley.
The home side were quick to reduce the margin with a Davies penalty, and then went ahead on the 50 minute mark thanks to a Dion Jones try.
Davies followed up with another penalty chance before Ireland increased their tally with a well worked Tom Daly try who claimed the offload from Rory Scannell. With the wind stiffening across the pitch, the Lansdowne clubman watched his conversion effort tail away to the right of the posts.
Wales managed to steady themselves with a fourth successful penalty from Davies, moving them 17-12 clear with a quarter of an hour remaining.
After 76 minutes Tom Daley kicked a close-range penalty to set up a nail biting finish with two points the difference. But despite their best efforts Ireland were unable to claw back enough territory to get into scoring range again.
Wales' greater level of experience - they boasted eight of the squad that finished third at last summer's IRB Junior World Championship - helped them grind out a nervy victory in the end.
Ireland U20s now face England U20s this Friday night at Dubarry Park, ko 7.35pm.
Ireland U20s: Stuart Olding (Belfast Harlequins/Ulster); Alexander O'Meara (Hartpury/Exiles), Tom Daly (Lansdowne/Leinster), Rory Scannell (Dolphin/Munster), Rory Scholes (Belfast Harlequins/Ulster); Steve Crosbie (Old Belvedere/Leinster), Luke McGrath (UCD/Leinster) (capt); Brian Scott (UCC/Munster), George McGuigan (Newcastle Falcons/Exiles), Chris Taylor (Malone/Ulster), John Donnan (Ballynahinch/Ulster), Gavin Thornbury (UCD/Leinster), Peadar Timmins (UCD/Leinster), Ryan Murphy (Dolphin/Munster), Conor Joyce (Malone/Ulster).
Replacements used: Peter Dooley (Lansdowne/Leinster) for Scott (half-time), Jake Caulfield (Malone/Ulster) for Timmins (49-58 mins, temp sub), David Panther (Corinthians/Connacht) for O'Meara (69 mins), Darren Sweetnam (UCC/Munster) for Crosbie, John Andrew (Ballymena/Ulster) for McGuigan (both 76), Josh van der Flier (UCD/Leinster) for Timmins (78), John Creighton (Malone/Ulster) for McGrath (79).