The 59-year-old minister is expected to steady a ship on the rocks after Nene's state capture inquiry bombshells, where he admitted to a relationship and to meeting the controversial Gupta family at their Saxonwold home.
He then added that that Nene can no longer inspire much needed confidence to revive the economy.
His major achievement at the central bank was building the nation's foreign-exchange reserves to nearly 40 billion dollars from less than 10 billion dollars.
But Nene's opponents say he was involved in corrupt deals with the Guptas when he was deputy finance minister and head of the state pension fund.
He said no person should be above scrutiny and all relevant and credible accusations of wrongdoing should be thoroughly investigated.
Earlier this week, several economists expressed the view that there would not be major deviations to the mini budget if a new finance minister were to be appointed.
"He has indicated that there is risk that the developments around the testimony that he gave to the commission of inquiry into state capture would detract from the important task of serving the people of South Africa particularly as we [government] works to re-establish public trust in government", announced Ramaphosa.
Ramaphosa said he had received a resignation letter from Nene and had made a decision to accept it.
During his decade-long tenure as central bank governor, Mboweni established a reputation as a monetary-policy conservative - he was a fierce defender of inflation targeting, which was introduced the year after he took office, and raised the repurchase rate to 13.5% in 2002 to control price growth and boost the rand.
I am human too, and I make mistakes.
Last week Nene told an inquiry into government corruption he had made numerous visits to the Gupta family, friends of former leader Jacob Zuma accused of unfairly winning state contracts and influencing the firing of ministers.
The rand firmed to R14.7216 to the dollar in the moments leading up to the announcement‚ after earlier weakening to R15.0625 following reports that Mcebisi Jonas had declined the position.