The area was known to the Guanches, the first inhabitants of the island, as Añazo or Añaza. The famous Mummy of San Andrés is one of the most important archaeological remains of the aboriginal past of the region.

Besides caves with some remains of mummified animals and stones with engravings ruprestres. This area belonged to the Menceyato de Anaga (aboriginal Guanche kingdom of Anaga), one of nine in which the island was divided.

On 3 May 1494 Castilian troops under the control of the conqueror Alonso Fernández de Lugo disembarked on the beaches of the present city and founded a military camp that would eventually develop into the city. From this place began the conquest of the island of Tenerife. During the foundation, Alonso Fernández de Lugo placed a large wooden cross in reference to the day of disembarkation, during the Catholic festivity of the Invention of the Cross (3 May). After the conquest and defeat of the Guanche aborigines, the capital of the island was initially established in the city of San Cristóbal de La Laguna, which was founded in the same year of the conquest of the island in 1496.

Later, it became one of the most important ports of the Atlantic, a status it retains to this day. This former fishermen’s village rose to prominence after a Volcano destroyed the port of Garachico in the 18th century. Santa Cruz became the major port on the Island. It first won its independence from La Laguna and, in the 19th century, was awarded the status of Capital of the Province of Canary Islands by King Ferdinand VII.

Between 1833 and 1927 Santa Cruz de Tenerife was the sole capital of the Canary Islands. In 1927 a Royal decree ordered that the status of capital city of the Canary Islands would be shared with Las Palmas in Gran Canaria. This arrangement remains in place today.