Chikerema was born at Kutama Mission in Zvimba, in present-day Mashonaland West province; Robert Mugabe, who was his nephew, shared the same birthplace and the two were very close during childhood.
He argued for a referendum of all adults of Southern Rhodesia on whether it should have independence, and opposed the government's use of the House of Chiefs as a means of consulting African opinion.
When Ian Smith's government increasingly threatened a unilateral declaration of independence, Chikerema declared the willingness of ZAPU to take up armed struggle, promising "a campaign of terror" in which "at first we will attack white farms in isolated areas, and with the arms we capture there, we will attack white homes in the towns".
After the collapse of talks in Lusaka in December 1974, Chikerema on behalf of FROLIZI signed an agreement with Nkomo of ZAPU and Rev.
Chikerema participated in the internal settlement talks of 1978 and supported the proposal of reserving 28 seats for white voters in a majority-rule Parliament.
In July 1978 the Department of Information called a press conference at which a man appeared claiming to have been sent by ZIPRA (ZAPU's military wing) to assassinate four of the co-Ministers, including Chikerema.
James Chikerema together with Raymond Chinamora were the editors of a weekly liberation struggle newspaper called The Rise of Zimbabwe.
[3] On 29 June 1979 after Abel Muzorewa took over as prime minister, Chikerema led a group of seven members of the House of Assembly to split with him due to concerns about his lack of firmness.
He attained the status of 'elder statesman' and while he was not necessarily in line with the majority view, he was listened to with considerable respect based on his previous campaigns.