Slavery in New Spain was based mainly on the importation of slaves from Central Africa and West Africa to work in the colony in the enormous plantations, ranches or mining areas of the viceroyalty, since their physical constitution supposedly made them suitable for working in warm areas.

The largest slave traders in Mexican territory were the Portuguese and the English. The countries that controlled the transatlantic slave market in terms of number of slaves shipped were Great Britain, France, and Portugal.

In 1517, Charles V established a system of concessions by which his subjects in the Americas could use slaves, thus starting the slave trade. When the Spaniards settled in New Spain, they brought some Bantu African workers with them as slaves. For their part, the Dominican friars who arrived in America denounced the conditions of slavery for Native Americans. As did bishops of other orders, they opposed the unjust and illegal treatment before the audience of the Spanish king and in the Royal Commission afterwards.

A bull promulgated by Pope Urban VIII on 22 April 1639 prohibited slavery in the colonies of Spain and Portugal in America. The King of Spain Philip IV of Spain approved the prohibition against enslavement of Indigenous peoples, but allowed it for Bantu Africans. Many slaves gained freedom by escaping and taking refuge in the mountains of Orizaba, Xalapa, and Córdoba in the state of Veracruz, where they became known as Cimarrones, or maroons.

In addition to the Indians and the Spaniards, Africans constitute the third root of mestizo society in Mexico, which has its origin in New Spain. The international commercial exchanges of that period included humans. Europeans traded in Africa for captives taken in warfare, and began to export them to the Americas. Most of the African population arrived in New Spain as slaves, where they were used for heavy labor. Due to the reduction in the Indigenous population, primarily due to infectious diseases, but also warfare and social disruption, Europeans took millions of people from Africa to be used as enslaved laborers. They disrupted numerous societies by taking their young people in their prime. Many enslaved Africans died during what became known as the Middle Passage, and others in the New World because of harsh conditions, especially in Caribbean colonies and South America.

Slaves from Africa were considered the means to satisfy the demand for labor to develop new lands. Between 1521 and 1594, approximately 36,500 African slaves arrived on Mexican shores. Then from 1595 to 1622, 322 slave ships delivered 50,525 slaves to Mexican ports once again. These slaves represented almost half of the total number of slaves brought to the Spanish West Indies. By 1810, they were about 625,000 free (a differentiation often forgotten) and 10,000 slaves distributed throughout Mexico and along the coasts and in tropical areas. They worked on crops such as sugar cane but also in a variety of trades. Slave societies yielded high profits for the major planters.

Both male and female Africans were enslaved. Males were used for field labor, and physical trades. While women were sometimes used in the fields, they also filled numerous domestic service positions, acting as wet nurses, washerwomen, cooks, maids, seamstresses, or took personal care of masters and mistresses. Elite families usually had male servants to attend to the men.)

Slaves believed that complaining to the Holy Office might give them relief from their harsh conditions. In the absence of effective civil courts where a complaint of mistreatment could be filed, Afro-Mexicans saw the Inquisition as a way to alleviate this miserable situation.