Coombs will partner Ospreys clubman Ian Evans in the second row. Evans returns from injury to start the fixture.
The same back row that started the final autumn international against Australia will face Ireland with captain Sam Warburton combining with Aaron Shingler and Toby Faletau.
The front row sees the return of Adam Jones from injury and he links up with Matthew Rees and Gethin Jenkins to reunite the 2009 British & Irish Lions front row.
In the back-line, Dan Biggar is the only change to the side that kicked off last season's Six Nations with victory over Ireland in Dublin.
"As a squad we have worked hard over the past two weeks and go into Saturday excited and confident at defending our title," said interim head coach Rob Howley.
"It's a boost to have Adam and Ian return from injury and it's a great opportunity for Andrew who has been performing well at regional level to show what he can do on this stage.
"The Six Nations is all about momentum and we know we have to hit the ground running against Ireland."
WALES Team & Replacements (v Ireland, 2013 RBS 6 Nations Championship, Millennium Stadium, Saturday, February 2, kick-off 1.30pm):
Club/international Caps -
15 - Leigh Halfpenny (Cardiff Blues/39)
14 - Alex Cuthbert (Cardiff Blues/13)
13 - Jonathan Davies (Scarlets/30)
12 - Jamie Roberts (Cardiff Blues/47)
11 - George North (Scarlets/26)
10 - Dan Biggar (Ospreys/11)
9 - Mike Phillips (Bayonne/71)
1 - Gethin Jenkins (Toulon/94)
2 - Matthew Rees (Scarlets/56)
3 - Adam Jones (Ospreys/83)
4 - Andrew Coombs (Newport Gwent Dragons) *
5 - Ian Evans (Ospreys/25)
6 - Aaron Shingler (Scarlets/4)
7 - Sam Warburton (Cardiff Blues/33) (capt)
8 - Toby Faletau (Newport Gwent Dragons/21)
16 - Ken Owens (Scarlets/10)
17 - Paul James (Bath/39)
18 - Craig Mitchell (Exeter Chiefs/10)
19 - Olly Kohn (Harlequins) *
20 - Justin Tipuric (Ospreys/10)
21 - Lloyd Williams (Cardiff Blues/8)
22 - James Hook (Perpignan/66)
23 - Scott Williams (Scarlets/16)
* Denotes uncapped player