While the treatment of indigenous populations in the Spanish colonies shared some characteristics with apartheid, such as legalised social stratification and racial discrimination, it was not apartheid as understood in the 20th-century South African context. Apartheid was a system of institutionalised racial segregation and discrimination, enforced by law in South Africa from 1948 to the early 1990s. In contrast, the Spanish colonial system was more fluid, allowing for some social mobility through marriage and economic success, despite the existence of a deeply entrenched caste system. Nevertheless, the treatment of indigenous populations in Spanish colonies was characterised by severe exploitation and systemic inequalities based on race.

Under the Spanish colonial system, indigenous populations were often coerced into economic roles that supported colonial exploitation, primarily in labour-intensive sectors. They worked in mines extracting precious metals, a cornerstone of the colonial economy. They were also a significant workforce in agriculture, tasked with cultivating and harvesting crops critical to both local sustenance and exportation. Additionally, indigenous peoples were utilised for construction projects, including building roads and infrastructure that facilitated colonial expansion. This economic exploitation was justified by the colonial authorities through the paternalistic encomienda system, which, despite its supposed protective intentions, resulted in extensive abuse and mistreatment.

The Catholic Church's role in the treatment of indigenous peoples was often dualistic. On one hand, the Church was complicit in the colonial project, seeking to convert indigenous peoples to Christianity and sometimes using conversion as a justification for conquest. On the other hand, many clerics advocated for the humane treatment of natives, opposing the brutal methods of colonial administrators. Figures like Bartolomé de las Casas, who was a Dominican friar, actively campaigned against the maltreatment and advocated for the rights of indigenous populations. Thus, while the Church was a tool of assimilation and cultural domination, it also provided some of the most vocal criticism of colonial abuses.

Assimilation policies greatly impacted indigenous languages and education. The Spanish enforced a linguistic assimilation policy that prioritised Spanish as the language of administration, commerce, and religion, leading to a decline in the use of indigenous languages. Educational systems were established to indoctrinate indigenous peoples with Christian doctrine and Spanish cultural norms, often erasing local educational traditions and knowledge systems. As a result, many indigenous languages diminished in use or became extinct, and the loss of these languages entailed the loss of rich cultural and historical knowledge that they carried.

In the Spanish colonies, a complex caste system evolved, categorising individuals into distinct social classes. At the top were the 'Peninsulares', Spaniards born in Spain; followed by 'Criollos', Spaniards born in the colonies. Below these were the 'Mestizos' (mixed European and indigenous ancestry), 'Mulattoes' (mixed European and African), and other mixed groups. Indigenous peoples and Africans occupied the lowest positions. This stratification dictated one’s social status, job prospects, and legal rights. The indigenous were largely marginalised, and while some intermarriage occurred, leading to the rise of 'Mestizos', pure-blooded indigenous peoples generally suffered under the oppressive weight of colonial society.