The original inhabitants of the Gabon region were pygmies, hunter-gathers who have left little in the way of an archaeological record. What we do know of early humans in Gabon comes from stone age sites such as Njole (approximately 200 km east of Libreville), which have revealed stone age axes, pottery fragments and worked quartz pieces. These traces probably date back to the earliest waves of the Bantu Migration (around 500 BCE) originating from the region of west Africa now known as Cameroon.

Bantu-speaking groups in Gabon lacked writing and so our knowledge of their history is limited to what can be deduced from oral tradition and archaeology. The oral traditions of two groups in Gabon give approximate dates of much later in the Bantu Migration - the Mpongwe people (also known as Mahongwe) are said to have arrived during the 13th century, and the Fang around the end of the 18th century. Both groups came from the north, from what is now Cameroon and Equatorial Guinea. Pygmies still survive in small family groups in remote parts of Gabon.

In 1472 the merchants and sailors of Portuguese trading ships became the first Europeans to make contact with Gabon's inhabitants. The name Gabon comes from a Portuguese word for a particular style of coat with a hood which the estuary of the Komo River resembled. The Portuguese, however, preferred the islands of Bioko, São Tomé, and Príncipe, creating sugar plantations (which needed workers) and trading with the mainland. One group in particular formed trading ties with the Portuguese - the Vili, who had recently formed the decentralized proto-kingdom of Loango.

(Loango is considered by many Africanist historians to have been part of the much greater kingdom of Kongo.)

By the 1600s, European merchants were trading tobacco, cloth, iron implements, alcoholic drinks, and firearms for ivory, hardwoods, and rubber. They also started trading with local chieftains for slaves. Between the 1760s and 1840s, settlements on the Gabon estuary, as well as those on the coast to the south, became slaving hubs. Slaves were sent down river from Gabon's interior by African slavers and held in barracoons (enclosures, typically temporary in nature) to await the Dutch, British, and French slave ships. Slaves from Gabon were shipped mainly to Brazil and Cuba.

The majority of African groups in Gabon were involved in the slave trade. The Orungu, centered around Cape Lopez, maintained power through their control of the slave trade on the Ogooué River. The Mpongwe of the Gabon estuary also profited from the trade. The Vili of Loango dominated in the trade throughout southern Gabon. Oral traditions of the Fang suggest that they avoided the slave trade - but their warlike invasion of northern Gabon from the savannah lands of Cameroon drove previously settled groups ahead of them, straight into the arms of those African groups involved in slavery. It was the result of the Fang's advance which led to much of the depopulation of Gabon during the trans-Atlantic slavery era.

By the 1800s it was the French rather than the Portuguese who were the main European influence in Gabon. By 1815, the French had joined the British in halting the slave trade along Gabon's coast, and a new era of trade, exchanging manufactured goods for raw materials, was taking precedence.

The era of French colonialism was ushered in with the signing of two treaties with the Mpongwe on the banks of the Gabon estuary.