In 1972, he replaced Benedicto Kiwanuka as the leader of the Democratic Party, having previously served as his Parliamentary Secretary.

[5] Ssemogerere was a Presidential Candidate in the disputed 1980 General elections which were won by Milton Obote's Uganda People's Congress.

[2] After Yoweri Museveni became president in January 1986 following a coup, Ssemogerere was consecutively Minister of Internal Affairs (1986–88[2]), Foreign Affairs (1988–94) and Public Service (1994–95)[3] and at the same time held the post of Deputy Prime Minister in Museveni's National Resistance Movement government (from 1986).

[3] After his retirement from politics in November 2005, he was succeeded as party president by John Ssebaana Kizito, the mayor of Kampala at that time.

Their children include Grace Nabatanzi (1963–2011), who married Gerald Ssendaula; Karoli Ssemogerere, an American-trained lawyer; Anna Namakula, a public policy analyst with the Foundation for African Development, Immaculate Kibuuka, a fashion designer; and Paul Semakula an ICT Consultant.