The High Court in Cape Town ruled that the administration had failed to allow adequate public consultation for preliminary agreements with Russia, South Korea and the United States to build eight reactors.
Environmental groups led by Earthlife Africa had challenged the plan in court, saying the government had not properly evaluated the true financial costs and environmental impact.
Agreements with two other countries, China and France, were not affected by the ruling.
The country relies mainly on coal-fired power plants, with one nuclear plant.
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The government says the new reactors would supply an additional 9,600 MW of electricity, more than five times current nuclear output.
The plan, expected to cost about one trillion rand (USD 73 billion), was announced in 2010.
But credit agencies cited doubts about the affordability of the plan when downgrading South Africa's credit ratings to "junk" status in recent months.
"We are highly vindicated by the today's judgement. The rule of law has prevailed in this long and complex battle," said Earthlife Africa spokeswoman Makoma Lekalakala.