Gareth Thomas will lead Wales from full-back and veteran hooker Mefin Davies returns at hooker as the tourists look to level the Test series against Australia at the Suncorp Stadium in Brisbane on Saturday.
Thomas' move from the wing as he wins his 94th cap means no place for Neath-Swansea Ospreys' Lee Byrne, with coach Gareth Jenkins giving Newport-Gwent Dragons' Aled Brew the chance to lose the one-cap-wonder tag from his career record while Chris Czekaj switches to the right wing.
But up front Brent Cockbain's expectations of being fit to play against the country of his birth in his home state of Queensland have been dashed as he failed to recover from the head injury that forced him off in the 29-23 first Test defeat.
Michael Owen continues in the second-row after taking over from Cockbain in the 35th minute at Telstra Stadium while Leicester-bound Davies comes in for Matthew Rees, who has returned home to be with wife Becky for their birth of their first child.
Following his part in Wales' downfall in the dying seconds in Sydney, scrum-half replacement Gareth Cooper sees another former Bath man, Andy Williams, take over as cover for Mike Phillips.
And while Williams hopes to add to his four-cap Test record, three-times capped Cardiff Blues' openside Robin Sowden-Taylor has similar sentiments as he takes the place on the bench vacated by Owen's elevation to the starting line-up.
Jenkins was relieved to find centres Sonny Parker and Jamie Robinson fit for selection after hip injuries, but their partnership means no place in the starting line-up for Gavin Henson, who can expect to again see some action following his return to Test rugby last weekend.
Jenkins said: 'There were many positives for us to take out of our performance last week and the players will have renewed self belief on Saturday night.
Meanwhile, Australia coach John Connolly is boosted by the return of fly-half Stephen Larkham, while Western Force winger Digby Ioane will win his first Wallabies cap.
Larkham returns after recovering from a minor hamstring injury that forced his late withdrawal from last week's 29-23 win over Wales in Sydney, while Sam Norton-Knight, who filled in at number 10, drops out of the 22-man squad.
Lock Dan Vickerman will make his first appearance since November after recovering from a shoulder injury and replaces Mark Chisholm, who will start from the bench.
Benn Robinson starts at tighthead prop in front of Waratahs team-mate Matt Dunning, George Smith takes over from Phil Waugh at openside flanker, while 21-year-old Ioane will partner Drew Mitchell on the wing.
Julian Huxley retains his place at full-back, while Brumbies utility back Mark Gerrard returns to the bench, with Scott Staniforth dropping out of the squad.
Stirling Mortlock has been named as captain in Waugh's absence and will again partner Adam Ashley-Cooper in the centres, while Matt Giteau retains the scrum-half starting role ahead of veteran George Gregan.
Wales: Gareth Thomas (Toulouse, captain); Czekaj, Robinson (both Cardiff Blues), Parker (Neath-Swansea Ospreys), Brew (Ospreys); Hook, Phillips (both Ospreys); I Thomas (Llanelli Scarlets), Davies (Leicester), A Jones (Ospreys), Owen (Newport-Gwent Dragons), Sidoli (Cardiff), Charvis (Newport-Gwent), J Thomas (Ospreys) Gavin Thomas (Llanelli).
Replacements: Jones (Harlequins), Hibbard (Ospreys), Morgan (Cardiff), Sowden-Taylor (Cardiff), Williams (Newport-Gwent), Sweeney (Newport-Gwent), Henson (Ospreys).
Australia: Julian Huxley; Digby Ioane, Stirling Mortlock (captain), Adam Ashley-Cooper, Drew Mitchell; Stephen Larkham, Matt Giteau; Wycliff Palu, George Smith, Rocky Elsom, Dan Vickerman, Nathan Sharpe, Guy Shepherdson, Stephen Moore, Benn Robinson.
Replacements: Adam Freier, Matt Dunning, Mark Chisholm, Stephen Hoiles, Phil Waugh, George Gregan, Mark Gerrard.