Wales, beaten 41-13 by world champions South Africa at Twickenham two weeks ago, thrashed the Wallabies 40-6 at last year's World Cup - but only three starters from that clash in Lyon will back up at the Sydney Football Stadium on Saturday.
Thomas - an inside centre at club level - will play outside his Cardiff teammate Ellis Bevan, the halfback who made his debut against the Springboks.
Hathaway gets his chance on the right wing with Liam Williams moving to fullback and Aaron Wainwright making his 50th appearance for Wales at No.8.
Hooker Dewi Lake will again captain the side from the front row alongside Sydney-born prop Archie Griffin, who gets his first Test start at tighthead in place of the injured Keiron Assiratti.
Gatland has chosen a new second row in Dafydd Jenkins and Christ Tshiunza, while Tommy Reffell returns at openside flanker for James Botham after missing the South Africa loss through injury.
Wales have not won a Test against the Wallabies in Australia since 1969 and their opponents will be keen to hit the ground running in their first match under new coach Joe Schmidt.
"This first Test is going to be a great challenge for us," Gatland said.
"Test matches are all about fine margins and we know we need to be accurate, keep our discipline and stay in the fight for the full 80 minutes.
"There's a lot of talent within the Australia squad and we know they will want to come out firing and put in a performance against us this weekend."
Wales squad:
15. Liam Williams, 14. Josh Hathaway, 13. Owen Watkin, 12. Mason Grady, 11. Rio Dyer, 10. Ben Thomas, 9. Ellis Bevan, 8. Aaron Wainwright, 7. Tommy Reffell, 6. Taine Plumtree, 5. Dafydd Jenkins, 4. Christ Tshiunza, 3. Archie Griffin, 2. Dewi Lake (capt), 1. Gareth Thomas.
Replacements: 16. Evan Lloyd, 17. Kemsley Mathias, 18. Harri O'Connor, 19. Cory Hill, 20. James Botham, 21. Kieran Hardy, 22. Sam Costelow, 23. Nick Tompkins.
