"Minister Mthembu was an exemplary leader, an activist and life-long champion of freedom and democracy. He was a much-loved and greatly respected colleague and comrade, whose passing leaves our nation at a loss," Ramaphosa added.
On January 11 Mthembu tweeted that he had contracted Covid-19.
"Today I visited the Military hospital in Tshwane to get medical attention for an abdominal pain. After undergoing some tests, I tested positive for Covid-19," he said.
Mthembu then thanked the South Africans who wished him a speedy recovery and said the country "must overcome Covid-19."
John Steenhuisen, the leader of the Democratic Alliance, which is the opposition party in South Africa, said he was "devastated" to learn about the minister's passing.
"Was such an honour to serve alongside this true South African patriot. Condolences to his family and friends and the colleagues in his party," he said in a tweet
As of Wednesday South Africa's Department of Health reported 1,369,426 cases of Covid-19 and 38,854 deaths.
Ramaphosa extended coronavirus restrictions
in the country on January 11, citing a "massive increase" in Covid-19 cases driven by a variant discovered there last year.
In addition to extending the existing measures, Ramaphosa announced that 20 land borders will be closed until February 15.
He was harassed and intimidated by apartheid police and during the Bethal terrorism trial was charged with sabotage, treason and terrorism, but was acquitted, according to South African presidency website
Under President Nelson Mandela
, he was the ANC party spokesperson from 1995-1997 and again from 2009-2014.