The opening of the Embassies located in Mexico and Ghana, a few years after the establishment of diplomatic relations on 8 August, 1961, allowed the promotion of political ties between both countries. However, the Government of Ghana decided to close its Diplomatic Mission in 1972 while Mexico did the same later in 1980.

The former Ambassador of Mexico to Nigeria, Marco Antonio García Blanco, presented his credentials to the Government of Ghana, as a concurrent country on 21 May, 2013. On that occasion, the then President John Dramani Mahama stated the interest of his country in strengthening relations of friendship and cooperation with Mexico. 

In 2013, the Embassy of Mexico in Nigeria sent a verbal note to the Ministry of Foreign Affairs and Regional Integration of Ghana announcing the decision to open an Embassy in the capital Accra. In November 2013, and once the Ghanaian government gave its initial consent, the then Secretary of Foreign Affairs, Jose Antonio Meade Kuribreña, gave the instruction to open the Embassy in Ghana, under the same building of the Pacific Alliance (Chile, Colombia, and Peru).

In 2014, the Mexican Foreign Ministry sent to Accra the designated official from the Mexican Foreign Service, César Dante López Arredondo, who was accredited as Chargé d'Affaires, a.i., in order to make the necessary preparations to open the Embassy. 

On January 13, 2015, the Ministry of Foreign Affairs and Regional Integration of Ghana announced the agrément in favor of H.E. Maria de los Angeles Arriola Aguirre as the Ambassador of Mexico to the Republic of Ghana. This decision was transmitted to the Mexican Secretariat of Foreign Relations in February, 2015.

Amb. Maria de los Angeles Arriola Aguirre initiated her duties as Head of Mission in April 2015.