The town is well known for its colonial architecture and its contributions to Colombian cultural and political life. It is also known as the "white city" due to the color of most of the colonial buildings in the city center, where several churches are located, such as San Francisco, San José, Belén, Santo Domingo, San Agustín, and the Catedral Basílica Nuestra Señora de la Asunción, known locally as "La Catedral". The city's cathedral was home to the Crown of the Andes, a 16th-century Marianist devotional object featuring emeralds taken from the captured Inca Emperor Atahualpa. It was sold to finance local health care institutions.
Popayán has been home to seventeen Colombian presidents, as well as noted poets, painters, and composers. The University of Cauca (est. 1827), one of Colombia's oldest and most distinguished institutions of higher education, is located here, so Popayán is also known as the "University City". Nearby is Puracé National Natural Park. The nearest large city is Cali, in the Valle del Cauca Department, north of Cauca.
Much of the city's original splendor was destroyed on 31 March 1983, when an earthquake toppled many buildings. Though many were rebuilt and repaired, the heart of the city still has ruins and empty lots. In 2005, Popayán was declared by the UNESCO as the first city of gastronomy because of its variety and meaning to the intangible patrimony of Colombian culture. The culinary history of the Cauca Department was chosen because it maintains traditional food preparation methods that have been passed down orally for generations. In 2009, UNESCO also declared the Semana Santa processions during Easter Week a Masterpiece of the Oral and Intangible Patrimony of Humanity.
The word Popayán comes from an indigenous language. There are different theories about the origin of this word, one claims it means: Po: "Two"; pa: "reed"; yan: "village", or; "Two villages with reed roofs". Another theory says that the word Popayán comes from the name of the indigenous cacique, called Payán, who used to live around Eme Hill, nowadays known as Las Tres Cruces Hill. Yet another theory says that according to the historian Arcecio Aragón, the origin of the word Popayán is "Pampayán" from the Quechua language: pampa (valley) and yan (river), thus, the "valley of the river", where "river" refers to the Cauca River.