In August municipal elections the ANC suffered its worst losses since taking power when apartheid fell in 1994.
The foundation set up to guard the legacy of the late Nelson Mandela on Tuesday blamed South Africa's President Jacob Zuma for the "wheels coming off" Africa's most industrialised nation and urged a change in political leadership.
Since coming to power in 2009, Zuma has survived a string of corruption scandals almost unscathed. But South Africa has had to bear the cost of his antics as investors worry about its political stability, business climate and rule of law.
The non-profit Nelson Mandela Foundation, whose board consists of ten prominent South African academics, politicians and journalists, called on the African National Congress (ANC), the liberation movement once headed by Mandela and now led by Zuma, to change its leadership.
"We call on the governing party to take the steps necessary to ensure that the vehicle of state be protected and placed in safe and capable hands," it said in a rare statement entitled: "Time to account for crippling the state".
Zuma's spokesman did not answer a phone call seeking comment.
Several ANC members have called for the 74-year-old to quit but the ANC's top echelons have backed him. In August municipal elections the ANC suffered its worst losses since taking power when apartheid fell in 1994.
Opposition parties and civic groups are planning to march in the capital Pretoria on Wednesday to demand, among other things, that he resign.
In a blow to Zuma and the ANC, Ndileka Mandela, a grandchild of Mandela, backed the foundation's stance.
"As Grandad always said, if the ANC does what the apartheid government did, you have every right to do what we did to the apartheid government," she said. "That statement could never be more true than now with what we are seeing happening."
But Zuma has shown no signs of stepping down before his second and final term as president is up in 2019, despite corruption scandals damaging him both financially and politically.
In March, the Constitutional Court ordered him to repay some of the $16 million spent on enhancing his Nkandla home in rural KwaZulu-Natal province. But Zuma weathered a motion of no-confidence in parliament over the scandal and has since paid back more than $500,000.
The Mandela Foundation said the court ruling over Nkandla was an example of how Zuma had failed to uphold the constitution. "It is increasingly a national consensus that he has failed the test," it said.
Zuma is also entangled in a scandal around the alleged political influence of a trio of wealthy brothers. About a hundred protesters chanted slogans against Zuma outside a court in Pretoria where his lawyers were trying to delay the release of a report on the matter.
The president also faced accusations of meddling after fraud charges against Finance Minister Pravin Gordhan were unexpectedly dropped on Monday.
Near record unemployment and a stagnant economy have exacerbated discontent with Zuma's government, which also failed to end weeks of often violent student demonstrations over the cost of university education.
The Mandela Foundation said it had seen a weakening of law enforcement bodies under Zuma and supported "the demand to hold to account those responsible for compromising our democratic state and looting its resources."