Djotodia was born in Vakaga, French Equatorial Africa (modern day Central African Republic), reportedly in 1949. He is Muslim, and as such part of a religious minority in the mostly Christian Central African Republic. He lived in the Soviet Union for about 10 years. While there he studied, became fluent in Russian, got married and had children. When he returned to Vakaga he was regarded as an intellectual, well-educated man who spoke various languages. Although he was noted for being politically ambitious he was an obscure figure, little known outside his native region, and worked in the civil service. He was a tax official during the 1980s.
Having studied economic planning in the Soviet Union, Djotodia worked at the Central African Republic's Ministry of Planning and subsequently at the Ministry of Foreign Affairs. He served for a time as Consul in the Sudanese city of Nyala.
Djotodia soon became involved in a milieu of rebel activity; he was one of the founders and leading members of the Union of Democratic Forces for Unity rebel group in 2006. He lived in exile in Cotonou, Benin during the war. In November 2006 he was arrested together with his spokesman Abakar Sabon without trial by Beninese forces at the behest of the government of Central African President François Bozizé. They were released in February 2008 after agreeing to participate in peace talks with the CAR government.
In December 2012, Djotodia was a key leader in the Séléka rebel coalition when it succeeded in rapidly taking control of a large portion of the country. At peace talks in January 2013, President Bozizé agreed to appoint a prime minister from the opposition and incorporate the rebels into the government. Following negotiations, a national unity government, headed by Prime Minister Nicolas Tiangaye, was appointed on 3 February 2013; it was composed of Bozizé supporters, the opposition, and rebels. Djotodia received the key post of First Deputy Prime Minister for National Defense.
The peace agreement unraveled in March 2013, as Séléka resumed seizing towns, accusing Bozizé of failing to keep his promises. The rebels kept their five ministers, including Djotodia, from going to Bangui. Djotodia said that rebel soldiers made the decision, not himself. There was speculation that, while Djotodia may have been content with his prominent new government post, others in Séléka wanted to take power outright. After days of fighting, the rebels captured Bangui on 24 March 2013, forcing Bozizé to flee the country, and Djotodia declared himself President. Djotodia said that there would be a three-year transitional period and that Tiangaye would continue to serve as Prime Minister.
Djotodia promptly suspended the constitution and dissolved the government, as well as the National Assembly. He then reappointed Tiangaye as Prime Minister on 27 March 2013. Top military and police officers met with Djotodia and recognized him as President on 28 March 2013. A new government headed by Tiangaye was appointed on 31 March 2013; Djotodia retained the defense portfolio.
On 3 April 2013, African leaders meeting in Chad declared that they did not recognize Djotodia as President; instead, they proposed the formation of an inclusive transitional council and the holding of new elections in 18 months, rather than three years as envisioned by Djotodia. Speaking on 4 April, Information Minister Christophe Gazam Betty said that Djotodia had accepted the proposals of the African leaders; however, he suggested that Djotodia could remain in office if he were elected to head the transitional council. Djotodia accordingly signed a decree on 6 April for the formation of a transitional council that would act as a transitional parliament. The council was tasked with electing an interim president to serve during an 18-month transitional period leading to new elections.
The transitional council, composed of 105 members, met for the first time on 13 April 2013 and immediately elected Djotodia as interim President; there were no other candidates. A few days later, regional leaders publicly accepted Djotodia's transitional leadership, but, in a symbolic show of disapproval, stated that he would "not be called President of the Republic, but Head of State of the Transition". According to the plans for the transition, Djotodia would not stand as a candidate for President in the election that would conclude the transition.
In the months that followed Séléka's takeover, the group was criticized for continuing to perpetrate violence against civilians. Djotodia was formally sworn in as President on 18 August 2013. On that occasion he said that he hoped to be "the last of my countrymen to have to take up arms in order to come to power". He also vowed that he would not stand as a presidential candidate.
Sectarian violence between Muslims and non-Muslims continued to escalate, and Djotodia faced pressure from regional leaders and the international community due to his apparent inability to control the situation. Djotodia resigned as President at a summit held in N'Djamena on 10 January 2014. He then went into exile in Benin on 11 January. He was welcomed at Cotonou Airport by Benin's Foreign Minister Nassirou Bako Arifari, who said that Benin received Djotodia "at the request of member states of the Economic Community of Central African States" as a "contribution to the search for peace in central Africa."
Seleka announced in July 2014 that Djotodia had been restored as leader of the group.