President Jacob Zuma has abused the trust of South Africans and "he must go, sooner, rather than later", the Nelson Mandela Foundation said on Tuesday.
"He must go because he has demonstrated that he is not fit to govern. We call on the state to hold him accountable for his actions. Some things cannot be pardoned," the foundation said in a statement.
The foundation has called on Zuma to step down, in order to "shore up" the governing party's election prospects for 2019.
"It is 14 months since the Nelson Mandela Foundation first called for President Zuma to resign. We have now reached a point where South Africans can no longer wait for him to do so."
The foundation said it has watched, from December last year, "sometimes in disbelief, as the floodgates of testimony have opened".
"Hearings, investigations, enquiries and other forms of disclosure are providing overwhelming evidence that systematic looting by patronage networks linked to President Zuma have betrayed the country Nelson Mandela dreamed of as he took his first steps of freedom 28 years ago," it added.
It said time was of the essence: "To delay now, will lead to more of the ugly scenes of violent conflict we saw yesterday (Monday). We call for calm and respect for the rule of law during all protest actions related to the president."
The foundation was referring to clashes during two protests outside the party's headquarters, Luthuli House. Black First Land First (BLF) movement members, who were marching in support of Zuma, clashed with the ANC's anti-Zuma supporters.
However, it warned: "It would be a mistake, of course, to think that the removal of one person will address what is now deep-rooted and systemic corruption. The challenge is to identify and uproot multiple networks at different levels."
Meanwhile, the foundation has applauded the work that has already been done by the ANC and the state in fighting corruption.
"This work will require years of endeavour and we call on all South Africans to commit to supporting it. The Nelson Mandela Foundation is making that commitment."