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Running in lane four, Mhlongo, who holds the world record of 11.00, started strong out the blocks and surged ahead of the field, crossing the finish line with a season's best 11.12.
Mhlongo finished ahead of Cuba's Yamel Vives Suarez in second (11.20) while Eddy Bernard of Malaysia came in third (11.58).
READ | SA's Paris hero Mhlongo hopes 100m gold will 'open the floodgates for our country'
Mhlongo, who carried South Africa's flag at the opening ceremony, bagged his first Paralympic medal in his second Games.
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