It is exempt, i.e. immediately subject to the Holy See (not part of any ecclesiastical province) and depends on the missionary Roman Congregation for the Evangelization of Peoples.

Its cathedral episcopal see is the Catedral María Inmaculada, dedicated to Mary Immaculate, in the city of Mitú, in Vaupés Department.

On 9 June 1949 Pope Pius XII established the Apostolic Prefecture of Mitú on territory split off from the Apostolic Vicariate of Los Llanos de San Martín.

It lost split-off territory on 19 January 1989 when the Apostolic Vicariate of San José del Guaviare (now a diocese) was created.

On 19 June 1989 Pope John Paul II elevated it to a Vicariate Apostolic (entitled to a titular bishop) and named it the Apostolic Vicariate of Mitú-Puerto Inírida.