The first zambos were initially the offspring of escaping shipwrecked slaves, as well as plantation slave escapees, who ventured into various Central American, South American and Caribbean jungles seeking refuge in remote Amerindian communities to hide and escape capture by colonial authorities. An example would be on the island of Hispaniola (the present day Haiti & the Dominican Republic), in which some escaped slaves encountered the few remaining Tainos on the island.

Racial mixing occurred on the island and today Afro-Amerindians make up a small percentage of the populations of both Haiti and the Dominican Republic. These Amerindians — themselves under threat from encroaching European colonizers — were sympathetic to the plight of the fleeing slaves and welcomed them into their communities, offered them food and sanctuary, and in many cases also their daughters as wives.

As in the United States during slavery, there are instances in Latin American history of Africans and Amerindians joining together and forming free renegade encampments to fight their European colonizers and slaveholders. In Latin America, these primarily African settlements of runaways, or Maroons, were called quilombos.

The most famous of all quilombos is the legendary Palmares in Brazil, which at the height of its flourishing had a population of over 30,000. The word "Zambo" later became a racist word used to describe individuals of African descent.

The history behind the African ancestry of the Garifuna is usually attributed to escaping shipwrecked slaves, whereas for the Zambos of north-western South America, the Lobos of Mexico and most other Zambos in general are attributed to escaping plantation slaves.

Officially, Zambos represent small minorities in the northwestern South American countries of Colombia, Venezuela, and Ecuador. A small but noticeable number of zambos resulting from recent unions of Amerindian women to Afro-Ecuadorian men are not uncommon in major coastal cities of Ecuador.

Prior to the rural to urban migration, the Amerindian and Afro-Ecuadorian ethnicities were mostly constrained to the Andes region and province of Esmeraldas respectively. The communities that exist in Brazil, mainly along the northwestern region of the country, are known as Cafuzos.

In Honduras, they are known as Garifunas, and while Zambos can also be found in other Caribbean and Central America countries such as the Dominican Republic, Belize and Nicaragua) their history and origins are not linked to that of the Garifuna. In Mexico, where they were known as Lobos, literally meaning wolf, they formed a sizeable minority in the past. The great majority of Lobos have now been absorbed into the much larger Mexican Mestizo population and can only be found in tiny communities scattered around the southern coastal states, such as Michoacán, Guerrero, Oaxaca, Campeche, Quintana Roo, and Yucatán, most notably the state of Veracruz and the Costa Chica, incidentally the same locales where the country's Afro-Mexicans reside.

Culturally, Mexican Lobos followed Amerindian traditions rather than African ones, as is also the case in Bolivia, where the Afro-Bolivian community has absorbed/retained many aspects of Amerindian culture, such as dress and use of the Aymara language.