The starting XV features three uncapped players - winger Patience Mokone, No.8 Faith Tshauke and Anushka Groenewald at flank.
A further five uncapped players have been named on the replacements' bench in props Anuchka Ekron and Sinothile Bhengu, lock Dineo Ndlhovu, flanker Nobuhle Mjwara and centre Leigh Fortuin.
Fortuin and Mokone represented the Springbok Women's Sevens team earlier in the season, while all of the uncapped players, apart from Mjwara, also played for the Junior Springbok Women earlier in their careers.
Sharks Women loose forward Mjwara was part of the Springbok Women WXV 2 training squad last year and attended recent alignment camps.
In a serious show of intent, South Africa will start with five backs who represented the country at the previous Rugby World Cup in New Zealand, while Nomawethu Mabenge, who scored the team's first try of the tournament against France in their opener match in 2022, will come off the bench in Antananarivo.
For good measure, Mabenge was also the leading try scorer in the Madagascar tournament in 2023.
Qolo will become the 11th player to captain the Springbok Women in 21 years of international rugby and said she was happy with the preparations going into the first match.
"The squad have been progressing and focusing on the main job, which is to retain the trophy," she said.
"Our set peace has been our main focus and if we add that to our skill set in the backs, we will deliver a good performance."
Springbok Women assistant coach Franzel September agreed with his captain and said they are expecting a physical battle and some direct rugby.
"What we saw in our analysis is that they are not scared to run with the ball, so there is an element of variety in their play, and they love doing quick taps from penalties," he said.
"We prepared well and will be ready for everything they are going to throw at us."
September insisted that the team's focus will be on themselves and what they want out of this match: "We know what we want to do and how to do it. We pride ourselves in our set-piece to secure go forward ball and that will not change just because we have some new players in the squad."
September said the system will prevail ahead of individual performances: "Some players will be desperate to impress with Rugby World Cup selection on the horizon, but we will look at how players compliment and strengthen the system, rather than them doing individual things."
In a late change to the squad, Anja le Roux was deemed medically unfit to travel to Madagascar. She will be replaced by Vianca Boer, who is due to join the squad on Friday. The Springbok Women's Sevens player represented the Leopards Women in 2024 before joining the national sevens squad in Stellenbosch. She is uncapped at Test level.
Kickoff at Stade Makis in Antananarivo is at 12:00.
Springbok Women: 15 Byrhandre Dolf, 14 Simamkele Namba, 13 Chuma Qawe, 12 Aphiwe Ngwevu, 11 Patience Mokone, 10 Mary Zulu, 9 Unam Tose, 8 Faith Tshauke, 7 Lerato Makua, 6 Anushka Groenewald, 5 Anathi Qolo, 4 Nomsa Mokwai, 3 Nombuyekezo Mdliki, 2 Luchell Hanekom, 1 Xoliswa Khuzwayo.
Replacements: 16 Roseline Botes, 17 Anuchka Ekron, 18 Sinothile Bhengu, 19 Dineo Ndlhovu, 20 Nobuhle Mjwara, 21 Felicia Jacobs, 22 Leigh Fortuin, 23 Nomawethu Mabenge.