Opposition leaders immediately accused President Paul Kagame of ordering his assassination.
The opposition coalition Rwandan National Congress said Patrick Karegeya, a former colonel and longtime Kagame ally in war who turned against him in peace, was found strangled in a room at Johannesburg's plush Michelangelo Towers hotel. It is believed Mr Karegeya was strangled after he was found in the hotel room on a bed with a swollen neck. A towel with blood and a rope were found in the room's safe.
Congress co-ordinator Theogene Rudasingwa said it is unclear if Mr Karegeya was killed on Tuesday or Wednesday. He said Mr Karegeya's death follows a pattern of assassinations ordered by Mr Kagame.
Mr Kagame's government has vehemently denied such charges, though Rwandan exiles say British, US and Belgian law enforcers have frequently warned them that their government is plotting to kill them.
Gunmen twice tried to kill Mr Kagame's former chief of army staff, Lt Gen Faustin Kayumba Nyamwasa, while he was living in exile in Johannesburg in 2010.
Mr Rudasingwa said Mr Karegeya had gone to the Johannesburg hotel to meet a Rwandan man who had posed as a friend of the opposition. Mr Karegeya, who was 53, leaves a wife and three children.