In a televised statement he said he was quitting with immediate effect but said he disagreed with his ANC party's decision.
The ANC had told him to step down or face a vote of no confidence in parliament.
The 75-year-old has been facing calls to give way to Deputy President Cyril Ramaphosa, the ANC's new leader.
Mr Zuma, who has been in power since 2009, faces numerous allegations of corruption.
Earlier on Wednesday, police swooped on the Johannesburg home of the powerful and wealthy Gupta family with whom Mr Zuma has close ties.
He began his speech by laughing and joking with members of the press, asking them why they looked so serious.
After paying tribute to those whom he had worked with over the years, Mr Zuma said that violence and division within the ANC had influenced his decision to step down.
"No life should be lost in my name and also the ANC should never be divided in my name. I have therefore come to the decision to resign as president of the republic with immediate effect," he said.
"Even though I disagree with the decision of the leadership of my organisation, I have always been a disciplined member of the ANC.
"As I leave I will continue to serve the people of South Africa as well as the ANC, the organisation I have served... all of my life."
BBC
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