Justin Tipuric will captain Wales for the first time in Sunday's World Cup clash against Uruguay.
Ospreys flanker Tipuric leads a team showing 13 changes from the side that beat Fiji on Wednesday, with only wing Josh Adams and centre Hadleigh Parkes remaining.
Adams, who scored a hat-trick of tries against Fiji, suffered a dead leg during that match but is fit to resume.
Starting for the first time in this tournament will be players including wing Hallam Amos, centre Owen Watkin, scrum-half Aled Davies, lock Bradley Davies and a fit-again Adam Beard.
Ospreys second-row forward Beard returns to action a month after undergoing appendix surgery that delayed his arrival in Japan.
Aaron Wainwright, who started Wales' opening two World Cup games at blindside flanker, switches to number eight alongside Tipuric and Aaron Shingler.
Wales head coach Warren Gatland has opted for a split of six forwards and two backs on the replacements' bench, with scrum-halves Gareth Davies and Tomos Williams providing back division cover.
Victory for Wales against Uruguay would result in them topping Pool D with four successive wins - their best World Cup group stage performance since 1987.
It would also confirm a quarter-final appointment with Six Nations rivals France in nine days' time.
France finished as runners-up in Pool C following the cancellation of Saturday's game against England due to the approach of Super Typhoon Hagibis.
Wales team to play Uruguay
Forwards: 1 Nicky Smith (Ospreys), 2 Ryan Elias (Scarlets), 3 Dillon Lewis (Cardiff Blues), 4 Bradley Davies (Ospreys), 5 Adam Beard (Ospreys), 6 Aaron Shingler (Scarlets), 7 Justin Tipuric (CAPTAIN, Ospreys), 8 Aaron Wainwright (Dragons)
Backs: 9 Aled Davies (Ospreys), 10 Rhys Patchell (Scarlets), 11 Hallam Amos (Cardiff Blues), 12 Hadleigh Parkes (Scarlets), 13 Owen Watkin (Ospreys), 14 Josh Adams (Cardiff Blues), 15 Leigh Halfpenny (Scarlets)
Replacements: 16 Elliot Dee (Dragons), 17 Rhys Carre (Saracens), 18 Wyn Jones (Scarlets), 19 Jake Ball (Scarlets), 20 Ross Moriarty (Dragons), 21 James Davies (Scarlets), 22 Tomos Williams (Cardiff Blues), 23 Gareth Davies (Scarlets)