Born and raised in Bamako, Keïta began a career as a teacher in 1936 under French colonial rule before entering politics during the 1940s.

In 1945, he co-founded the Sudanese Union (US) with Mamadou Konaté which became part of the African Democratic Rally (RDA) the following year to form the US-RDA.

As President, Keïta soon established the US-RDA as the only official party, and began implementing socialist policies based on extensive nationalization.

In foreign affairs, Keïta supported the Non-Aligned Movement and maintained strong relations with the West despite his socialist leanings.

A leading Pan-Africanist, he played important roles in the drafting of the charter of the Organization of African Unity and the negotiation the 1963 Bamako Accords, which ended the Sand War between Morocco and Algeria.

His family were Malian Muslims who claimed direct descent from the Keita dynasty, the founders of the medieval Mali Empire.

While the coalition was led by Félix Houphouët-Boigny, Keïta assumed the post of RDA Secretary-General in French Sudan, and head of the Soudanese affiliate: the US-RDA.

[2] As a socialist, he led his country towards the progressive socialization of the economy; at first starting with agriculture and trade, then in October 1960 creating the SOMIEX (Malian Import and Export Company), which had a monopoly over the exports of the products of Mali, as well as manufactured and food imports (e.g. sugar, tea, powdered milk) and their distribution inside the country.

He travelled to the United States after the 1st Summit of the Non-Aligned Movement in Belgrade, FPR Yugoslavia where the conference delegated him with expressing their common positions to the American administration.

He also resolved the Conflict between Morocco and Algeria and would also try to form a union between Ghana, and Guinea and worked tirelessly to improve relations with the countries of Senegal.

The first post-independence elections, in 1964, saw a single list of 80 US-RDA candidates returned to the National Assembly, and Keïta was duly reelected to another term as president by the legislature.

On 19 November 1968, General Moussa Traoré overthrew Modibo Keïta in a coup d'état, and sent him to prison in the northern Malian town of Kidal.

After being transferred back to the capital Bamako in February 1977 in what was claimed to be an action by the government towards national reconciliation in preparation for his release,[6] Modibo Keïta died, still a prisoner, on May 16, 1977.

In 1963, he invited the king of Morocco and the president of Algeria to Bamako, in the hope of ending the Sand War, a frontier conflict between the two nations.