Mnangagwa had the correct political credentials: he fought beside Mugabe during the 1970s to liberate Zimbabwe from white minority rule and since independence in 1980 has held a host of Cabinet positions as a loyal member of the ruling Zanu-PF party.
But last Wednesday, Mnangagwa fled into exile, two days after being sacked by Mugabe for "disloyalty, disrespect, deceit and being unreliable".
Mnangagwa's firing is seen as clearing the way for Grace Mugabe to succeed her husband as leader of Zimbabwe.
On the weekend before Mnangagawa's sacking was officially announced, she publicly mocked the vice-president at a rally and later called on her husband to let her take over Mnangagwa's post.
Mnangagwa though has vowed not to back down. "I will return to Zimbabwe to lead you," he said in a five-page statement released on Wednesday.
He issued a direct challenge to Mugabe, saying that the ruling Zanu-PF wasn't "personal property of you and your wife to do as you please."
After Zimbabwean independence in 1980, Mnangagwa was the feared minister of State Security, accused of directing crackdowns on opposition supporters which saw thousands killed in the Matabeleland and Midlands provinces.
He also has the backing of the powerful war veterans association and the country's generals.
War veterans leader, Chris Mutsvangwa, a strong ally of the former vice-president, said that Mugabe's "conduct was making a crime of Zanu-PF" and was against the will of the people.
Speaking at a press conference in South Africa on Wednesday, Mutsvangwa said the war veterans were appealing to all Zimbabweans to stop Mugabe and his wife, calling them a "total threat" to democracy.
"We are all united as Zimbabweans and we are coming across the board, the MDC [Movement for Democratic Change], the churches, everyone has come together to address the menace that Zimbabwe now faces with Mugabe - a senior old man with a mad wife."
This is a complete about-face for the war veterans, those who fought in wars against white rule in the 1970s.
The former fighters have traditionally backed Mugabe, a former guerrilla leader who had ruled Zimbabwe since being elected president in 1980.
Political analyst Takura Zhangazha told DW he thought the possibility of intervention by the country's military or war veterans was extremely unlikely.
"I don't think there is any other route except the political route, even though the official [war veteran] associations have said they are behind the [former] vice president," Zhangazha said .
The question is though whether Mnangagwa will try to agitate from within the Zanu-PF party, or whether he will align with the opposition in an effort to unseat Grace.
Joice Mujuru, who was ousted as vice president in 2014 in a similar internal Zanu-PF power struggle, has reached out to Mnangagwa with a peace offering.
Mujuru launched the Zimbabwe People First's party in 2016 as a challenge to Mugabe.
"It is time to redeem yourself and walk out of this falling dynasty‚" she said in a statement. "Together we can build another great Zimbabwe not driven by love for power and money."
Zimbabwe's opposition, which has formed an alliance to take on Mugabe in 2018's much-anticipated elections, doesn't look like its benefitting from Zanu-PF's political battles.
"The opposition is not in a very strong position in any way," analyst Zhangazha said.
"There may be opportunities to galvanise their supporters but I don't think it will change much."
And as for Zanu-PF, the wrangling isn't over yet. The party is due to hold an extraordinary congress in December. One of the items on the agenda is to reinstate a quota for women.
If passed, this could cement Grace's power.
"The power struggles will continue until there is finality in respect to the successor question," political scientist Eldred Masunungure said in an interview with DW's AfricaLink programme.
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