The 25-year-old on Saturday clocked one minute and 55.28 seconds to beat Burundi's Francine Niyonsaba by 1.21 seconds, Xinhua news agency reported.
Kenya's Margaret Nyairera Wambui pocketed bronze in a personal best of 1:56.89.
It was Semenya's second Olympic medal after her silver medal in the 800m at the London 2012 Games.
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