Matfield will become the most-capped Test player in the history of South African rugby
There are two changes to the Springbok team to face Wales in Nelspruit, with prop Tendai 'Beast' Mtawarira and lock Flip van der Merwe in the starting line-up.
Mtawarira returns at loosehead prop, with Gurthrö Steenkamp reverting to the bench, while Flip van der Merwe will partner captain Victor Matfield in the second row in the place of Bakkies Botha.
The only other change to the team is amongst the backline reserves, where Wynand Olivier replaces the injured Johan Goosen to provide necessary midfield cover. Ruan Pienaar will provide backup for scrumhalf and flyhalf, while Lwazi Mvovo can cover fullback and wing.
Matfield will become the most-capped Test player in the history of South African rugby when he leads the Springboks against Wales in his 112th Test match at the Mbombela Stadium.
Matfield made his Test debut on 30 June 2001 against Italy in Port Elizabeth. He retired after the World Cup in 2011 on 110 caps, but made a highly successful return to the game earlier this year.
"This is a fantastic accolade for Victor," said Springbok coach Heyneke Meyer on Wednesday.
"He has been a terrific servant of the game in South Africa and has led his country with distinction since returning to the Green and Gold.
"When he returned to the game earlier this season, he set his goals on becoming a Springbok yet again and he’s worked extremely hard to get there. I don't think anyone can doubt that he deserves his place in the team and he's also been a great interim captain, with Jean de Villiers out injured."
Commenting on the team selection, Meyer said it was an easy decision to stick with the core of the team which beat the Welsh last weekend in Durban.
"I've always preferred to stick with a winning combination and the changes to the team were both part of our planning," said Meyer.
"The backline really performed well last weekend and we would like to give them another opportunity to play together, as there were a number of new combinations.
"The same applies up front. Bakkies is fit for selection, but we decided to manage his workload this week and I know Flip, who has been outstanding in the last two seasons, will slot back in easily. The same goes for 'Beast', who upped the tempo with his work rate last weekend."
Meyer said he is expecting another tough challenge from Wales this weekend.
"They've had another week together and will be keen to lift their game on Saturday, but at the same time we were not happy with certain aspects of our game and we’ve worked hard to rectify that," said Meyer.
"This is their last match of the season, so we're expecting them to come out firing. But we also want to make a step up and ensure we keep on improving as the season progresses."
South Africa: 15 Willie le Roux, 14 Cornal Hendricks, 13 JP Pietersen, 12 Jan Serfontein, 11 Bryan Habana, 10 Morné Steyn, 9 Fourie du Preez, 8 Duane Vermeulen, 7 Willem Alberts, 6 Francois Louw, 5 Victor Matfield (captain), 4 Flip van der Merwe ,3 Jannie du Plessis, 2 Bismarck du Plessis, 1 Tendai Mtawarira.
Replacements: 16 Schalk Brits, 17 Gurthrö Steenkamp, 18 Coenie Oosthuizen, 19 Lodewyk de Jager, 20 Schalk Burger, 21 Ruan Pienaar, 22 Wynand Olivier, 23 Lwazi Mvovo.
Date: Saturday, June 21
Venue: Mbombela Stadium, Nelspruit
Kick-off: 15.00 (13.00 GMT; 14.00 BST)
Referee: Steve Walsh (Australia)
Assistant referees: Romain Poite (France), Francesco Pastrana (Argentina)
TMO: Glenn Newman (New Zealand)