The key N3 highway linking Johannesburg and the east coast city of Durban was one of the worst affected and several portions were closed, with even detours impassible, officials said.
Emergency services were working to reach people in their vehicles but it was still not clear how many were affected and in what condition they were, N3 Toll Concession operations manager Thania Dhoogra told the ENCA broadcaster.
"Emergency services have been working flat out through the night. They have been attempting to reach as many roads users as they can," Dhoogra said.
Blankets and meals had been delivered to some stranded motorists, the government of the KwaZulu-Natal province said in a statement at midday.
Trucks had been parked on the side of the road since Friday, Road Traffic Management Corporation communications officer Simon Zwane told AFP. "Buses travelling between provinces have been stuck at petrol stations for around seven hours," he said.
Motorist Muhammad Goolam told the Newzroom Afrika channel that he had spent the night in his car with his children outside the town of Harrismith, around 270 kilometres (170 miles) southeast of Johannesburg.
"Over 13 hours, food supplies out, I don't see us managing to drive out of here without any assistant from emergency personnel," he said.
Some areas had seen up to two metres (six feet) of snowfall, the Arrive Alive road safety campaign said in a post on X.
South Africa's Border Management Authority said it had closed three border posts with the kingdom of Lesotho as "the current conditions pose a significant danger."
More snow was expected with second-highest orange warnings in place for several parts of the country, South African Weather Services forecaster Luthando Masimini told AFP. "It's an extreme case," he said.
Away from the danger areas, the rare phenomenon drew people excited to see the snow. Justin Nadasem Baker drove for three hours from Johannesburg with his family to Warden, about 50 kilometres from Harrismith.
"It was a three-hour drive. We are excited. It has been many, many years since we saw snow," he told AFP.
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