Lacey, 41, was also in charge of the Boks' Rugby Championship clash against Argentina at Loftus Versfeld in August this year. The Boks won 13-6.
Saturday's Test will be his 11th to date.
Lacey will be assisted by compatriot George Clancy and France's Pascal Gauzère. Graham Hughes of England will be the TMO.
Kick-off in Cardiff will be at 16:30 SA time.
Irish referee for Wales v Boks
Cape Town - Ireland's John Lacey will referee Saturday's Test between Wales and the Springboks at the Millennium Stadium in Cardiff.