Mpofu, previously the Governor of Matabeleland North Province, was appointed as Minister of Industry and International Trade in mid-April 2005, following the March 2005 parliamentary election. At the beginning of 2014, Mpofu was reported to be seeking nomination from ZANU-PF’s Matabeleland North provincial leadership for the position of party Chairman. It was reported that his main rival for the position was the Speaker of the Zimbabwean Parliament, Jacob Mudenda. It is believed that Mpofu was one of the earliest ZPRA guerillas to be trained for the Zimbabwean Liberation War way back in the 1960s.
Mpofu masterminded the freeze of basic commodities in Zimbabwe in mid-2007. He was appointed by Robert Mugabe to lead the price monitoring regime that was created following the price-freeze. He withdrew operating licenses from abattoirs across the country during the price freeze, a situation that resulted in beef becoming scarce in shops across the country. In early 2008, he initiated the idea of 'people's shops' government run retail shops that would sell products at cheap prices.
Sino-Zimbabwe trade
Mpofu was at the forefront encouraging trade between Zimbabwe and China, as part of the government's Look-East policy. At one time, Gao Hucheng, Chinese vice-minister for commerce, after meeting with Mpofu claimed: "Chinese goods had been well received by Zimbabweans and that his government would continue to promote trade between the two countries as this had also improved the lives of people."
Obert Mpofu was nominated again as the ZANU-PF candidate for the House of Assembly seat from Umguza constituency in the March 2008 parliamentary election. Mpofu was initially endorsed as unopposed, but Mark Mbayiwa challenged this in court and was successful in getting Mpofu's unopposed endorsement overturned. Campaigning in Umguza, Mpofu singled out Simba Makoni as an agent of western imperialism.. Mpofu won the seat, receiving 7,065 votes and defeating two candidates of the two Movement for Democratic Change factions, Cornelius Mbayiwa and Edmund Masuku, who respectively received 2,846 and 2,120 votes. He also defeated Mark Mbayiwa, who ran as an independent and received 555 votes.
Mpofu was appointed as Minister of Transport and Infrastructure in February 2014 and served until 2015.
Minister of Macro-Economic Planning and Investment Promotion
Mpofu was Minister of Macro-Economic Planning and Investment Promotion from 2015 until 2017.
Minister of Home Affairs
Following the dissolution of the Cabinet of Zimbabwe in 2017, it was announced that Robert Mugabe's successor Emmerson Mnangagwa had allowed only Patrick Chinamasa and Simbarashe Mumbengegwi to remain as acting ministers of Finance and Foreign Affairs respectively until the appointment of a new cabinet. However, Mpofu was appointed as Minister of Home Affairs and Culture in the new cabinet. Mpofu was later removed from the Mnangagwa Cabinet in September 2018.
