Bradman Best and Keaon Koloamatangi will earn their Origin debuts as part of seven changes to the side that lost 32-6 in Origin II last month.
Of those left out, only injured centre Tom Trbojevic and Payne Haas were unavailable, with the latter succumbing to an ankle injury he has been battling since May and aggravated playing for Brisbane on Saturday night.
Five-eighth Luai and prop Paulo are the most established of Fittler's players to lose their spots, having previously not missed a game through form since making their debuts in 2021 and 2020 respectively
Debutant prop Stefano Utoikamanu and starting second-rowers Hudson Young and Tyson Frizell have also been cut for the series finale to be played at Sydney's Accor Stadium on July 12.
Middle forwards Reagan Campbell-Gillard and Jacob Saifiti have earned recalls in place of Utoikamanu and Paulo, with Manly's 15-time Blue Jake Trbojevic also coming into the side.
Trbojevic played his first game back from a long-term calf injury on Sunday and is the latest NSW player to come into camp on the back of limited game-time.
In his first Origin game since 2020, in-form Eels captain Gutherson will play a utility role from the bench as Fittler looks to avoid the interchange dilemmas that haunted the Blues in Origins I and II.
The Blues named Nicho Hynes as a utility for Origin I but only played him for 12 minutes late on, and then deployed veteran hooker Damien Cook as a centre in the second game after injury struck Tom Trbojevic down.
Best's inclusion comes as the biggest surprise.
Fresh from scoring a hat-trick in the 66-0 shellacking of Canterbury, the Newcastle centre beat Bulldogs co-captain and two-time Origin representative Matt Burton in the race to replace Trbojevic.
South Sydney centre Campbell Graham had been considered the front-runner to slot into the centres but was ruled out with the same sternum injury that forced him to withdraw as 18th man for game one.
The NRL's leader in try assists, South Sydney five-eighth Walker will partner Eels halfback Mitch Moses in the halves for his fifth Origin appearance.
Walker most recently featured in all three matches of 2020's post-season series.
Joining him in the side for a maiden Blues appearance is Souths teammate Koloamatangi.
An ankle injury scuppered the back-rower's chances of earning a debut in the series opener but he has long been considered a future Origin player, most recently earning seleciton as 19th man for Origin II.
James Tedesco has retained his spot as fullback and captain despite concerns over his form and stiff challenges from Dylan Edwards and Scott Drinkwater in recent weeks.
Drinkwater has been named 18th man, with Panthers prop Spencer Leniu joining him on the extended bench.
NSW Blues: 1. James Tedesco (capt) 2. Brian To'o 3. Stephen Crichton 4. Bradman Best 5. Josh Addo-Carr 6. Cody Walker 7. Mitchell Moses 8. Jake Trbojevic 9. Damien Cook 10. Reagan Campbell-Gillard 11. Liam Martin 12. Keaon Koloamatangi 13. Cameron Murray 14. Isaah Yeo 15. Jacob Saifiti 16. Reece Robson 17. Clint Gutherson 18. Scott Drinkwater 19. Spencer Leniu.
