In 1987 he became assistant lecturer of mathematics at the University of Bangui and was vice-dean of the University's Facility of Science from 1989 to 1992. In the latter year he became director of the teachers' training college. He joined the Inter-State Committee for the Standardisation of Mathematics Programs in the French-speaking countries and the Indian Ocean (CIEHPM) in 1999, serving as the President of the Committee from 2001 to 2003. He became Vice-Chancellor of the University of Bangui in May 2004. Touadéra subsequently served a rector of the university between 2005 and 2008 during which he launched several key initiatives, such as the entrepreneurship training program and the creation of the Euclid Consortium.
Touadéra was appointed Prime Minister by President François Bozizé on 22 January 2008, following the resignation of Élie Doté. His government, composed of 29 members—four ministers of state, 17 ministers, and seven minister delegates, along with himself—was appointed on 28 January.
A national dialogue was held in December 2008, and Bozizé then dissolved Touadéra's government on 18 January 2009 in preparation for the formation of a government of national unity. Touadéra was reappointed as Prime Minister on 19 January. Later on the same day, his new 31-minister government was appointed, with only 10 ministers retaining their posts; many former rebels were included in the new lineup to prepare the country for the 2009 local elections and the 2010 presidential and parliamentary polls.