"No life should be lost in my name and also the ANC should never be divided in my name," he said during a nationally televised political address Wednesday. "I have therefore come to the decision to resign as President of the republic with immediate effect."
The announcement came after the ANC took the extraordinary step of calling for a no-confidence vote in the leader on Wednesday, a day after it publicly demanded his resignation
. Party officials on Tuesday decided to issue a "recall" notice after failing privately to convince Zuma that he should step aside.
After his resignation announcement, Zuma said he disagreed with the decision of his political party and that he has 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 organization I have served all of my life in," Zuma said.
Zuma, 75, survived multiple attempts by opposition parties to oust him during his more than eight years in power, earning him the nickname of the "Teflon president."
The ANC had been trying to push Zuma out for months. It dumped him as party president in December, narrowly electing Cyril Ramaphosa, a millionaire former union leader, over Zuma's preferred successor, his ex-wife, Nkosazana Dlamini-Zuma.
Ramaphosa said Sunday that the uncertainty over Zuma's future had damaged the ANC.
But despite signs that the party was losing electoral support over the protracted drama, internal divisions forced Ramaphosa to tread cautiously. For years, the ANC -- which led South Africa out of apartheid -- put party unity first, even as it became apparent that Zuma was an electoral liability.
The ANC said it wanted to "salute the outstanding contribution he has made and express its profound gratitude to him for the role he has played in the African National Congress spanning over 60 years of loyal service."
It acknowledged mistakes were made but praised his "legacy of delivery."
The party said it was accepting his resignation and expects each ANC member to cast a vote for Ramaphosa as its candidate for president.
CNN's Angela Dewan wrote from London.