The rights groups want Lt-Gen Nyamwasa to face trial in France or Spain.
Two human rights groups have asked a South African court to revoke the refugee status of former Rwanda army chief Faustin Kayumba Nyamwasa.
They argue he does not qualify as he has been accused of committing alleged crimes during his time in the army.
Lt Gen Nyamwasa fled to South Africa in 2010 after falling out with his former ally, Rwandan President Paul Kagame.
Months later he survived an assassination attempt, in which Rwanda denied any involvement.
The Consortium for Refugees and Migrant Rights in South Africa, supported by the Southern Africa Litigation Centre, have asked the High Court in Gauteng province to strip Lt Gen Nyamwasa of his refugee status.
South Africa’s immigration authorities granted him refugee status in June 2010 “despite the existence of substantial and credible allegations linking him to war crimes and crimes against humanity in both Rwanda and the Democratic Republic of Congo”, the rights groups said in a statement.
“Refugee law is intended to protect the persecuted – not the persecutor.”
Lt Gen Nyamwasa’s lawyer Kennedy Gihana told the BBC’s Focus on Africa programme that he was not worried about the legal action because South Africa’s authorities considered all the facts before giving his client refugee status.
“There is no grounds why they [the human rights groups] can compel the court to review the decision,” he said.
Last year a Rwandan military court sentenced Gen Nyamwasa to 24 years in jail for threatening state security.
Rwanda has pushed South Africa to extradite him to serve the sentence.
Lt Gen Nyamwasa has also been indicted by the French authorities for the shooting down of the plane carrying Rwanda’s former President Juvenal Habyarimana in 1994, while a Spanish indictment implicates him in the commission of war crimes and crimes against humanity committed in DR Congo, including the murder of 2,500 Hutu refugees, the rights groups said.
The general should not be sent back to Rwanda, where he faces threats against his life, but should face trial in France or Spain, they say.
Prior to their falling out, Lt Gen Nyamwasa and the Rwandan president had been close allies.
He helped Mr Kagame to come to power and was appointed army chief of staff in 1998.
But their relationship soured and he was accused of undermining Mr Kagame, who critics say runs a repressive regime.