Migiro served as a ward member of Chama Cha Mapinduzi from 1994 to 2000, and as a member of a Regional Executive Council from 2000 to 2005. From 2000 to 2006, she was the Minister of Community Development, Gender and Children's Affairs. She became the Minister of Foreign Affairs and International Cooperation on 4 January 2006, when the previous foreign minister, Jakaya Kikwete, who had been elected president, appointed his new cabinet. She was the first woman in that position since the independence of the United Republic of Tanzania.