Rassie Erasmus, director of rugby, said the Springboks have to regain their momentum and decided to give first appearances in the competition to nine players, while Makazole Mapimpi and Lukhanyo Am are the only players retained from the 23-13 reverse against New Zealand.
In addition, six of the opening day starting XV re-appear on the bench - including captain Siya Kolisi - while all of last Saturday's replacements (with the exception of the injured Jesse Kriel) are in the starting line-up.
The starting XV features nine of those who started the opening match of the international season; a 35-17 victory over Australia in the Rugby Championship in July.
One of the newcomers to the starting line-up is Brits, who moves to a new role in the back-row at number eight.
Brits captains the team for the second time having led the Springboks in the 24-18 victory over Argentina in Pretoria.
Frans Steyn, Francois Louw and Tendai Mtawarira all make second appearances against Namibia - having played in the Rugby World Cup meeting eight years ago - to provide a spine of experience to a team which has another five players yet to reach double figures in caps (Warrick Gelant, Sbu Nkosi, Mapimpi, Herschel Jantjies and Kwagga Smith).
Brits would cover the replacement hooker position and Franco Mostert (lock) would cover the loose forward positions along with Kolisi, who continues his rehabilitation with more planned game time from the bench.
Thomas du Toit, who only arrived in Nagoya on Tuesday as an injury replacement for Trevor Nyakane, goes straight into the matchday 23 as a front-row replacement.
South Africa: 15 Warrick Gelant, 14 Sbu Nkosi, 13 Lukhanyo Am, 12 Frans Steyn, 11 Makazole Mapimpi, 10 Elton Jantjies, 9 Herschel Jantjies, 8 Schalk Brits (c), 7 Kwagga Smith, 6 Francois Louw, 5 Lood de Jager, 4 RG Snyman, 3 Vincent Koch, 2 Bongi Mbonambi, 1 Tendai Mtawarira
Replacements: 16 Steven Kitshoff, 17 Thomas du Toit, 18 Eben Etzebeth, 19 Siya Kolisi, 20 Franco Mostert, 21 Cobus Reinach, 22 Damian de Allende, 23 Cheslin Kolbe
Date: Saturday, September 28
Venue: City of Toyota Stadium, Toyota City
Kick-off: 18:45 local (10:45 BST, 09:45 GMT)
Referee: Mathieu Raynal (France)
Assistant Referees: Nic Berry (Australia), Andrew Brace (Ireland) TMO: Graham Hughes (England)