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It took the Springboks just a few moments to make their extra man count, with Pietersen spotting an opening out wide to race down the wing and ground the ball in the corner.
Bryan Habana had a couple of opportunities to become the outright leading try-scorer in Rugby World Cup history, but the winger could not get the grounding right while trying to leap over, before being tackled short later in the half.
Cubelli tried to create something to get the Pumas back into the match as he returned from his spell off the pitch, but the two-time world champions quickly won the ball back, while Handre Pollard kicked three penalties before the interval to give South Africa a commanding lead heading into the break.
Argentina finally got off the mark at the start of the second half as Nicolas Sanchez slotted the ball over with a drop goal attempt from 40m out.
South Africa soon punished their opponents down the other end though as Habana continued to look for the record-breaking try, but realised Etzebeth was in a better position, setting him up to power over for the second try of the night.
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Pollard could not add the conversion, but split the uprights a few minutes later after Argentina were penalised for too many offsides.
Sanchez kicked again to reduce the gap to 18 points with 30 minutes remaining, but South Africa seemed happy to let their opponents have the ball while continuing to hold such a big lead.
The Pumas looked weary as full time approached, but their second-half efforts were rewarded with a late try as Juan Pablo Orlandi managed to stretch the ball over from a metre out for a consolation.