Flyhalf Pat Lambie and inexperienced scrumhalf Cobus Reinach come in for Handre Pollard and Francois Hougaard, though Meyer said they had not paid the price for disappointing performances in last weekend's 29-15 defeat by Ireland in Dublin.
World Cup winners JP Pietersen and Schalk Burger start on the wing and flank ahead of Cornal Hendricks and Teboho Mohoje, while Adriaan Strauss replaces Bismark du Plessis at hooker.
"We've accepted our performance against Ireland last weekend was not up to scratch and everyone in the touring squad has put up their hands and dug deep this week," Meyer said in a press release issued by South Africa rugby.
"We've really worked hard at fixing the mistakes we made and the challenge is now to put that into action on Saturday."
Meyer said the changes were not a knee-jerk reaction to the result in Dublin, but rather they were in line with rotational changes that he had in mind before the start of the tour.
Strauss, Lambie and Pietersen all started in the Springboks' last test at Twickenham, while Saturday's match will be Reinach's first in the starting team.
"Pat started at Twickenham for us two years ago and did very well," said Meyer.
"He's playing well at the moment and I wanted to give him the opportunity to start. Pat is tactically very astute and even though he's still pretty young, he's got a lot of experience.
"Adriaan, Schalk and JP have all started a number of tests this year and they will slot in easily -- we decided beforehand that we wanted to start all of these players in one of the first two tests on tour."
Meyer also gave his backing to Reinach with his scrumhalf options stretched thin with Fourie du Preez and Ruan Pienaar not available through injury.
"It's a big occasion for Cobus but he would not have been here if we didn't believe he could deliver the goods, and he'll be next to his provincial team mate in Pat.
"As usual, we're also expecting our replacements to raise the intensity when they're sent on and Bismarck, who had a very good game in Dublin especially in the set-pieces, 'Oupa' (Mohoje), Francois, Cornal and Handre will provide important cover off the bench."
Team: 15-Willie le Roux; 14-JP Pietersen, 13-Jan Serfontein, 12-Jean de Villiers (captain), 11-Bryan Habana, 10-Pat Lambie, 9-Cobus Reinach, 8-Duane Vermeulen, 7-Schalk Burger, 6-Marcell Coetzee, 5-Victor Matfield, 4-Eben Etzebeth, 3-Jannie du Plessis, 2-Adriaan Strauss, 1-Tendai Mtawarira
Replacements: 16-Bismark du Plessis, 17-Trevor Nyakane, 18-Coenie Oosthuizen, 19-Bakkies Botha, 20-Teboho Mohoje, 21-Francois Hougaard, 22-Handre Pollard, 23-Cornal Hendricks
