The 28-year-old Newport Gwent Dragons forward packs down in the second row alongside Ian Evans. Wales are shorn of injured locks Alun-Wyn Jones, Bradley Davies and Luke Charteris, while Evans has not started a game since November due to knee trouble.
Ospreys playmaker Dan Biggar, meanwhile, fills the fly-half role vacated by an injured Rhys Priestland as Wales look to end a seven-game losing run that represents their worst results sequence since 2003.
Interim head coach Rob Howley has resisted any temptation to field two openside flankers - skipper Sam Warburton and Justin Tipuric - with Warburton retained in his familiar number seven shirt, Aaron Shingler filling blindside duties and Tipuric on bench duty.
Former Wales captain Ryan Jones, who would have offered a back-row or second-row option, is sidelined after dislocating his thumb during the Ospreys' Heineken Cup game against Leicester 18 days ago.
Jones, hooker Richard Hibbard, backs Liam Williams and Eli Walker and lock Lou Reed were all unavailable for selection due to injuries.
Howley has reunited the 2009 British and Irish Lions Test front row of Gethin Jenkins, who wins his 95th cap, Matthew Rees and Adam Jones, with powerhouse scrummager Jones back in action after missing Wales' entire autumn series this season because of a knee injury.
And there is a role among the replacements for uncapped Harlequins lock Olly Kohn. Born in Bristol, 31-year-old Kohn has Welsh qualification through his late grandfather, who hailed from the Rhymney Valley.
Coombs' elevation to Test match status comes less than three years after he made his Dragons debut, and he only recently switched positions from back row to lock.
Coombs, a former computer software salesman, played Welsh Premiership club rugby with Pontypool and Newport before graduating into the Dragons' professional ranks.
But the Wales coaching staff have watched him closely, and he was among five newcomers announced earlier this month by Howley in the Six Nations squad.
"It's a great opportunity for Andrew, who has been performing well at regional level, to show what he can do on this stage," Howley said.
"As a squad, we have worked hard over the past two weeks and go into Saturday excited and confident at defending our title.
"The Six Nations is all about momentum, and we know we have to hit the ground running against Ireland."
Wales have not beaten another Test-playing country since defeating France at the Millennium Stadium last March to secure a third Six Nations crown and Grand Slam in eight years.
But they have defeated Ireland three times in a row, including a 2011 World Cup quarter-final victory, and field 10 starting XV survivors from the side that triumphed 23-21 in Dublin last season.
Wales: L Halfpenny (Cardiff); A Cuthbert (Cardiff), J Davies (Scarlets), J Roberts (Cardiff), G North (Scarlets); D Biggar (Ospreys), M Phillips (Bayonne); G Jenkins (Toulon), M Rees (Scarlets), A Jones (Ospreys), A Coombs (Newport Gwent Dragons), I Evans (Ospreys), A Shingler (Scarlets), S Warburton (Cardiff, capt), T Faletau (Newport Gwent Dragons).
Replacements: K Owens (Scarlets), P James (Bath), C Mitchell (Exeter), O Kohn (Harlequins), J Tipuric (Ospreys), L Williams (Cardiff), J Hook (Perpignan), S Williams (Scarlets).
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