Pope Leo X, believing the newly discovered land to be an island, by the papal bull Sacri apostolatus ministerio, dated 27 January 1518, created the Diocese of Yucatán, under the name Carolense and placed it under the protection of Our Lady of the Remedies (Santa Maria de los Remedios).

[3] The first resident bishop was Francisco Toral, a Franciscan friar, who took possession on 15 August 1562, one year after his appointment;[4] he assisted at the first and second Mexican Provincial Councils.

Juan Gómez de Parada, the 20th bishop, governed the dioceses of Yucatán, Guatemala, and Guadalajara with great success.

It was at the instance of Leandro Rodríguez de la Gala, his successor, that the new See of Tabasco was formed from parishes taken from the Diocese of Yucatán.

Believing that the colony of Belize was his dependency, the bishop sent missionaries there in 1864; this land, however, had been under the administration of priests sent form the Vicariate Apostolic of Jamaica since 1837.