Zuma has survived six previous no-confidence votes in parliament, but this is the first to be held by secret ballot after parliamentary speaker Baleka Mbete yesterday made the surprise decision to allow it.
Opposition parties hope it will encourage disgruntled legislators with the ruling African National Congress party to vote against Zuma, who has faced numerous allegations of graft while South Africa's economy has fallen into recession.
"Those MPs must recall that they are the representatives of the people, and must therefore represent the people in terms of what they do this afternoon," Mbeki told reporters.
The ANC holds a majority of the 400 parliament seats, and the party has repeatedly said its members will not support the opposition-led attempt to unseat the president. The party has 249 parliamentary seats, five of which are currently vacant, said a party spokeswoman, Nonceba Mhlauli.
"As you can see, thousands of people have reached the end of their tether in terms of what is happening in our beautiful country, our beautiful, diverse country that we should enjoy but we can't enjoy because millions of our people are without jobs," said one protester, Johnnie Jacobs.
If the motion succeeds, Zuma and his cabinet must resign immediately and Mbete will take over as acting president, according to Pierre de Vos, a constitutional expert and law professor at the University of Cape Town.
Last year, the Constitutional Court ruled unanimously that Zuma "failed to uphold" the constitution by not paying back some of the $20 million-plus in state money used to upgrade his rural home.
Zuma's ties to the Gupta family, immigrant businessmen accused of trying to manipulate government leaders and state companies for financial gain, also have stirred public anger.
The president's firing of widely respected finance minister Pravin Gordhan in a Cabinet reshuffle in March led two agencies, Fitch and Standard & Poor's, to lower South Africa's credit rating to below investment grade, or junk status.
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