The Wallabies will have a fresh look to their pack in San Salvador, with Allan Alaalatoa taking over the captaincy reins and loosehead prop Isaac Kailea earning his first Test start in two years against the Pumas.
Kiss has retained all of the backs who fired in the impressive home win over Japan earlier in August, but it will be all-change in the scrum for Saturday's (Sunday AEST) clash.
A powerful-looking back row of No.8 Rob Valetini, blindside flanker Tom Hooper, making his first start of the year, and openside Fraser McReight will team up, with captain Harry Wilson being rested while tighthead Alaalatoa takes the skipper's armband.
French-based Tupou, who scored three tries in two games against Japan, won't be available for the Wallabies' Bledisloe Cup campaign.
But he and second row enforcer Lukhan Salakaia-Loto have been left out as the coach - after some purposeful and brave selection calls against Japan - again assesses his options ahead of next year's Rugby World Cup.
"There's a way we're thinking to design it without being too cute," Kiss said, adding Tupou had a slight injury "situation" but he'd be fit to play next weekend in Mendoza.
"Taniela and Lukhan really went well, softened up the pack and the other boys came in and finished it off," he said of their big Townsville win.
"We're working in different ways and we've reshaped this one, for sure.
"We think it's worthwhile exploring this and we're balancing it out okay at the moment.
"We're trying to find out how deep we go in each position.
"It may not seem like order from what you're seeing, but it's making sense internally."
Josh Canham and Jeremy Williams resume their partnership in the second row, while Kiss goes again with the halfback duo of Ryan Lonergan and Carter Gordon, and the Queensland Reds centre pairing of Hunter Paisami and Isaac Henry, who combined nicely in the 56-17 win over Japan in Townsville.
It means Joseph-Aukuso Suaalii will return from a hamstring injury on the bench and star midfielder Len Ikitau won't play at all.
"(Suaalii) trained well; there's an opportunity to maintain some continuity in that midfield, keep it at its right place and utilise Joseph in any way we wish," Kiss said, adding his first option would be to deploy him in his usual No.13 position.
In a show of faith, Kiss said Wilson remained "the man" to captain the side but added now was the time to manage his workload and it would not cloud operations even with the embarrassment of backrow options available in the squad.
Saturday's match will be the first of a two-parter, with the second Test in Mendoza following on September 5, and is seen as an early acid test of the side under Kiss's leadership.
Argentinian coach Felipe Contepomi has kept the same starting line-up that went down 17-10 to South Africa, despite having to make 13 changes due to the absence of overseas-based players.
Santiago Carreras will wear the No.10 while Pablo Matera, winning his 125th cap, continues as captain in the absence of Julian Montoya.
Wallabies: Isaac Kailea, Brandon Paenga-Amosa, Allan Alaalatoa, Josh Canham, Jeremy Williams, Tom Hooper, Fraser McReight, Rob Valetini, Ryan Lonergan, Carter Gordon, Harry Potter, Hunter Paisami, Isaac Henry, Max Jorgensen, Tom Wright. Bench: Billy Pollard, Angus Bell, Massimo de Lutiis, Lachlan Shaw, Charlie Cale, Tate McDermott, Ben Donaldson, Joseph-Aukuso Suaalii.
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