In the continental region that is now Equatorial Guinea there are believed to have been pygmies, of whom only isolated pockets remain in northern Río Muni. Bantu migrations between the 17th and 19th centuries brought the coastal tribes and later the Fang. Elements of the latter may have generated the Bubi, who emigrated to Bioko from Cameroon and Rio Muni in several waves and succeeded former Neolithic populations. The Annobón population, native to Angola, was introduced by the Portuguese via São Tomé island (São Tomé and Príncipe).

The Portuguese explorer Fernão do Pó, seeking a path to India, is credited as being the first European to discover the island of Bioko in 1472. He called it Formosa ("Beautiful"), but it quickly took on the name of its European discoverer. The islands of Fernando Pó and Annobón were colonized by Portugal in 1474.

In 1778, the island, adjacent islets, and commercial rights to the mainland between the Niger and Ogoue Rivers were ceded to Spain in exchange for territory in the American continent (Treaty of El Pardo, between Queen Maria I of Portugal and King Charles III of Spain). Between 1778 and 1810, the territory of Equatorial Guinea depended administratively on the Viceroyalty of the Río de la Plata, with seat in Buenos Aires.

From 1827 to 1843, the United Kingdom established a base on the island to combat the slave trade, which was then moved to Sierra Leone upon agreement with Spain in 1843. In 1844, on restoration of Spanish sovereignty, it became known as the Territorios Españoles del Golfo de Guinea Ecuatorial. The mainland portion, Rio Muni, became a protectorate in 1885 and a colony in 1900. Conflicting claims to the mainland were settled by the Treaty of Paris (1900), and periodically, the mainland territories were united administratively under Spanish rule. Between 1926 and 1959 they were united as the colony of Spanish Guinea.

In September 1968, Francisco Macías Nguema was elected first president of Equatorial Guinea, and independence was recognised on October 12, 1968. In July 1970, Nguema created a single-party state. Nguema’s reign of terror led to the death or exile of up to 1/3 of the country's population. Out of a population of 300,000, an estimated 80,000 had been killed. The economy collapsed, and skilled citizens and foreigners left. Teodoro Obiang deposed Francisco Macías Nguema on August 3, 1979, in a bloody coup d'état.