Upon completing his education, Mogae returned to Botswana and embarked on a career in the government bureaucracy, serving in the Ministry of Finance and Development as a planning officer, as director of economic affairs, and as permanent secretary. He has also held a variety of posts in international organizations, including the International Monetary Fund (IMF), the African Development Bank, the International Bank for Reconstruction and Development, and the Commonwealth Fund for Technical Cooperation. In addition, he has served on the board of directors of several major corporations.
In January 1982, Mogae was named permanent secretary to the president and secretary to the cabinet in Masire's government. Ten years later, he was named minister of finance and development planning and in September 1992, amid a corruption scandal that forced the resignation of the vice president, Mogae was named vice president. He remained in that post, his reputation intact and untarnished by the scandals that periodically erupted within the administration, until 1998. On 31 March 1998, Masire stepped aside and Mogae became the third president of the Republic of Botswana; he won election in October 1999.