It will be the first time that the pair line up together for France since March 2025, with each one having suffered injuries since then.
"They are two top players who have won a lot with our team since 2020," said Galthie, who highlighted the benefit of the pair being club team-mates.
"Collective experience is important at this level and they have that, even though they haven't played much recently for France."
Scrum-half Dupont, 29, tore his cruciate knee ligament against Ireland in the 2025 Six Nations and when he returned to the national team in the following season's tournament, Ntamack, 27, was out injured.
In their absence, Bordeaux-Begles pair Maxime Lucu and Matthieu Jalibert, who is currently injured, had mostly lined up in the number nine and 10 jerseys.
It will be the 30th time that Dupont and Ntamack, aligned regularly at club level with Toulouse, match up as scrum-half and fly-half.
Galthie is missing a string of key players, mostly from Toulouse, including full-back Thomas Ramos, hooker Julien Marchand, locks Emmanuel Meafou and Thibault Flament, and back-rower Anthony Jelonch.
Toulouse centre Kalvin Gourgues is given his first start at centre, while tight-head prop Sipili Falatea and back-rower Cameron Woki make their first starts for Les Bleus since 2021 and 2023 respectively.
Francois Cros, normally a blindside flanker, was named at No.8, with Florian Verhaeghe and Mickael Guillard packing down in the second row.
After opening their campaign against Fiji on Saturday in Lyon, France go on to host South Africa six days later and conclude against Argentina on November 21, with both matches at the Stade de France.
"First and foremost, the Fijians have exceptional individual talent," said Galthie.
"We see it every weekend in our championship with their ability to surprise and be unpredictable.
"They love one-on-one duels, they're powerful, they're skillful... they're often the best players in their team, or the best finishers."
He added: "They are spectacular players and it will be a spectacular match."
France head up the northern hemisphere standings going into the business end of the Nations Championship, with Scotland, England and Ireland snapping at their heels.
France's sole loss in the opening away fixtures in July was a two-point defeat by New Zealand. Galthie's side followed that up by twice scoring 42 points in wins over Australia and Japan.
Fiji, meanwhile, are bottom of the southern hemisphere table having lost their opening three matches, including a 73-8 drubbing by England.
Nations Championship 2026
The inaugural Nations Championship will see six northern hemisphere and six southern hemisphere nations battle it out across six rounds in the July and November international windows before assembling in Twickenham for one unforgettable finals weekend on November 27-29.
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France team to face Fiji:
Starters: 15-Theo Attissogbe; 14-Aaron Grandidier-Nkanang, 13-Kalvin Gourgues, 12-Yoram Moefana, 11-Louis Bielle-Biarrey; 10-Romain Ntamack, 9-Antoine Dupont (capt); 8-Francois Cros, 7-Cameron Woki, 6-Paul Boudehent; 5-Mickael Guillard, 4-Florian Verhaeghe; 3-Sipili Falatea, 2-Maxime Lamothe, 1-Jean-Baptiste Gros
Replacements: 16-Peato Mauvaka, 17-Jefferson Poirot, 18-Regis Montagne, 19-Charles Ollivon, 20-Tom Staniforth, 21-Esteban Capilla, 22-Maxime Lucu, 23-Emilien Gailleton