At the crossroads of West Africa and Central Africa, the territory of what is now Cameroon has seen human habitation since some time in the Middle Paleolithic, likely no later than 130,000 years ago. The earliest discovered archaeological evidence of humans dates from around 30,000 years ago at Shum Laka. The Bamenda highlands in western Cameroon near the border with Nigeria are one of the most likely origin for the Bantu peoples, whose language and culture came to dominate most of central and southern Africa between 1000 BCE and 1000 CE.

European traders arrived in the fifteenth century and Cameroon was the exonym given by the Portuguese to the Wouri river, which they called Rio dos Camarões—"river of shrimps" or "shrimp river", referring to the then-abundant Cameroon ghost shrimp. Cameroon was a source of slaves for the slave trade. While the northern part of Cameroon was subject to influence from the Islamic kingdoms in the Chad basin and the Sahel, the south was largely ruled by small kings, chieftains, and fons.

Cameroon as a political entity emerged from the colonization of Africa by Europeans. From 1884, Cameroon was a German colony, German Kamerun, with its borders drawn through negotiations between the Germans, British, and French. After the First World War, the League of Nations mandated France to administer most of the territory, with the United Kingdom administering a small portion in the west. Following World War II, the League of Nations' successor, the United Nations, instituted a Trusteeship system, leaving France and Britain in control of their respective regions, French Cameroon and British Cameroon. In 1960, Cameroon became independent with part of British Cameroons voting to join former French Cameroon. Cameroon has had only two presidents since independence and while opposition parties were legalized in 1990 only one party has ever governed. Cameroon has maintained close relations with France and allied itself largely with Western political and economic interests throughout the Cold War and into the twenty-first century. This consistency gave Cameroon a reputation as one of the most stable countries in the region. In 2017, tensions between Anglophone Cameroonians in former British territory and the Francophone-dominated government led to an ongoing civil war known as the Anglophone Crisis in the west of the country, while Islamist insurgents Boko Haram continue to carry out military and terror attacks in the north of the country.

In January 2024, Cameroon launched the world's first routine malaria vaccine program, using the World Health Organization (WHO)-approved RTS,S vaccine developed by British drugmaker GSK. The initiative aims to save thousands of African children's lives annually. Despite some skepticism, health experts emphasize careful community outreach to combat vaccine hesitancy and stress the importance of using existing preventive measures alongside vaccines.

Archaeological research has been relatively scarce in Cameroon due to a lack of resources and transportation infrastructure. Historically the warm, wet climate in many parts of the country was thought of as inhospitable to the preservation of remains, but recent finds and the introduction of new techniques have challenged that assumption. Evidence from digs at Shum Laka in the Northwest Region shows human occupation dating back 30,000 years while in the dense forests of the south, the oldest evidence of occupation is around 7000 years old. Recent research in southern Cameroon indicates that the Iron Age may have started there as early as 1000 BCE and was certainly well established by 100 BCE at the latest.

Linguistic analysis, supported by archaeological and genetic research, has shown that the Bantu expansion, a series of migrations that spread Bantu culture across much of Sub-Saharan Africa, most likely originated in the highlands on the Nigeria-Cameroon border around 1000 BCE. Bantu languages spread with these people along with agricultural methods and possibly iron tools, first east and then south, forming one of the largest language families in Africa. In Cameroon, Bantu people largely displaced Central African Pygmies such as the Baka, who were hunter-gatherers and who now survive in much smaller numbers in the heavily forested southeast. Despite Cameroon being the original homeland of the Bantu people, the great medieval Bantu-speaking kingdoms arose elsewhere, such as what is now Kenya, Congo, Angola, and South Africa.

The earliest known civilization to have left clear traces of their presence in the territory of modern Cameroon is known as the Sao civilisation. Known for their elaborate terracotta and bronze artwork and round, walled settlements in the Lake Chad Basin, little else is known with any certainty due to the lack of historical records. The culture possibly arose as early as the fourth century BC but certainly, by the end of the first millennium BC, their presence was well established around Lake Chad and near the Chari River. The city-states of the Sao reached their apex sometime between the ninth and fifteenth centuries AD. The Sao were displaced or assimilated by the sixteenth century.

After the Muslim conquest of North Africa in 709, Islam's influence began to spread south with the growth of trans-Saharan trade, including in what is now northern Cameroon. The Kanem-Bornu Empire began in what is now Chad and likely came into conflict with the Sao. The Kanem Empire began in Chad in the eighth century and gradually extended its influence northward into Libya and southward into Nigeria and Cameroon. Slaves from raids in the south were their principal trade good along with mined salt. The Empire was Muslim from at least the eleventh century and reached its first peak in the 13th, controlling most of what is now Chad and smaller regions in surrounding countries. After a period of internal instability, the center of power shifted to Bornu with its capital at Ngazargamu, in what is now northwestern Nigeria, and territory was gradually reconquered and new territory in present-day Niger also conquered. The Empire began to decline in the seventeenth century though it continued to control much of northern Cameroon.