The building is located on the west side of Caldas Park in the historic center of the city of Popayán[3] (Cauca) in the South American country of Colombia.

In 1546, it was established the Diocese of Popayan by Pope Paul III in the Bull "Super speculates Militantis Ecclesiae" of September 1 of that year.

He was appointed as the first Bishop Juan del Valle, a native of Segovia (Spain).

The cathedral was, like all the buildings of Popayan, stripped of her immense artistic wealth by Antonio Nariño.

In addition, the historic area of Popayan (including the cathedral), was declared Colombia National monument by Law 163 of December 30, 1959.