[14][15] He then participated in the 1996 Ghanaian general elections as a parliamentary candidate for the Fanteakwa North constituency of the Eastern region of Ghana.
[20] He stood for the party National Organizer position,[3] and was appointed Ghana Minister for Local Government and Rural Development by President Mills during a cabinet reshuffle in January 2011.
[21] Prior to this appointment he had been the Eastern Regional Minister since the start of the Mills NDC government in 2009 and was succeeded by Kwasi Akyem Apea-Kubi.
[23][24] In November 2018, Ampofo was elected the National Chairman of the NDC at 9th delegate congress held at Fantasy Dome at the Trade Fair Centre in Accra.
[26] November 2020, the High Court of Ghana admitted into evidence alleged recordings of Ofosu-Ampofo committing criminal conspiracy.
The targeted individuals include the Electoral Commission (EC) chair and the Chairman of the National Peace Council among others This was after the court had rejected claims by lawyers for the politician that the audio breached constitutionally guaranteed right to privacy.