The Springboks, stunned 34-32 by Japan in their opening Pool B match last weekend, secured only their second win in seven test matches, with Schalk Burger, Schalk Brits and Bryan Habana also bagging tries.
Samoa flyhalf Michael Stanley slotted over two early penalties, but South Africa took a grip on the game after right wing Pietersen intercepted a lobbed pass by Stanley and raced more than half the pitch to score.
Flyhalf Handre Pollard kicked four penalties to give the Springboks a 17-6 halftime lead before they went on to demonstrate their true tournament credentials.
Pietersen was lucky to escape a yellow card on the stroke of halftime for pulling back Alesana Tuilagi with his outstretched hand at neck height but referee Wayne Barnes ruled the Samoan wing had gone down too easily.
The wing went over for his second try early in the second half thanks to quick handling by 2007 World Cup-winning scrumhalf Du Preez, Le Roux and De Villiers.
South Africa’s record try scorer Habana was itching to join him on the scoresheet but was pulled up short in the left corner and from the resulting throw-in, Du Preez moved the attack across to the right and Burger touched down on the hour.
Samoa looked to have reduced the deficit when replacement Tusi Pisi went over, only for the try to be disallowed for a forward pass.
Replacement forward Brits scored the bonus-point try for South Africa before Pietersen completed his treble with five minutes remaining and Habana had the final word when he raced over to score his 60th try for his country.
The three brothers of the Pisi family made World Cup history for Samoa when they took the field together in an otherwise forgettable afternoon for the Pacific Islanders.
(Additional reporting by John Geddie; Editing by David Goodman)
