The early history of Guinea-Bissau is obscure, but some of the major ethnic groups of the country, such as the Balante and Pepel, were apparently established there by the 12th century. The area was visited in 1446 by Nuno Tristão, a Portuguese slave trader, and became an important slave center. A Portuguese post was established at Bissau in 1687, but the Portuguese claim was disputed by the French and the British, and in 1792 the latter briefly had a settlement at Bolama. In 1879 the region was constituted a Portuguese colony, and border disputes with the French were settled by treaty in 1886. Not until 1915, however, were the Portuguese able to exercise effective control over the country.

For more than a thousand years the coast of Guinea-Bissau has been occupied by iron-using agriculturists. They were particularly skilled in the production of irrigated and dry rice and were suppliers of marine salt to adjacent areas of the western Sudan. From the 13th century coastal farmers came increasingly into contact with the outside world, first from the landward side and later from the seaward portion. The earliest recorded influences are associated with the dissolution of the Ghana empire when displaced peoples sought refuge near the coast. Later the region was loosely drawn into the sphere of the Mali empire, and regional governors called farims were appointed to impose some form of allegiance to the great Mande ruler.

The Portuguese territorial claim in Guinea was disputed by both the British and the French. Periodic negotiation first of all excluded the British (1870) and then settled the boundaries with the French-claimed territories (1886 and 1902–05). These frontier agreements were followed by the slow and sometimes violent imposition of Portuguese colonial rule. The final “pacification” campaigns were fought by João Teixeira Pinto in 1913–15. These wars were followed by nearly half a century of predominantly peaceful Portuguese administration. But with the rise of African nationalism after World War II and the gaining of independence by the neighbouring territories, Guineans again began to challenge their colonial rulers. Nationalist attacks on Portuguese administrative and military posts were instigated in July 1961 by guerrillas of the PAIGC, led by Amílcar Cabral. In August Cabral declared at Conakry, capital of the French-speaking Republic of Guinea, that political endeavours to obtain the liberation of Portuguese Guinea and the Cape Verde Islands from Portuguese domination would be replaced by armed struggle. Bitter guerrilla warfare ensued between the PAIGC National Liberation Army (about 10,000 men) and the Portuguese armed forces (about 30,000 strong). The guerrillas were unable to occupy the coastal towns and river ports, but by 1971 they were firmly established in the interior, especially in the areas adjacent to the republics of Senegal and Guinea.