Sebastián de Belalcázar, originally from Spain, became a key figure in the early colonization of South America during the age of exploration. After joining Francisco Pizarro's expedition in Peru and gaining fame through his conquests, he sought to expand Spanish territory further north into what is now Colombia. In his search for the fabled city of El Dorado, which was believed to be rich in gold and treasure, Belalcázar journeyed through the challenging Andean terrain. During this quest, he arrived at the fertile region of the Cauca Valley, a location ideal for establishment due to its resources and strategic trade advantages.

On July 25, 1536, he founded Santiago de Cali, named after Saint James and designed as a administrative capital of the region. The city was positioned to facilitate Spanish control over local indigenous tribes and access to vital trade routes. The founding of Cali marked a significant moment in the Spanish colonization efforts, serving as a base for further exploration and conquest in the mountainous interior of Colombia. The establishment also resulted in increased interaction with the indigenous populations, which would lead to cultural exchanges as well as confrontations.

The city quickly grew into an important center for the Spanish crown, reflecting the broader trends of colonization and the thirst for wealth and power in the New World. The motivations behind Belalcázar's expedition and the city's founding reflected the Spaniards' aspirations during this era, which encompassed exploration, conquest, and the spread of Christianity among indigenous peoples. The city of Cali today remains a vibrant testament to its historical roots and the impacts of Spanish colonization.