The islands were first discovered by Portuguese navigators between 1469 and 1472. The first successful settlement of Sao Tome was established in 1493 by Alvaro Caminha, who received the land as a grant from the Portuguese crown. Principe was settled in 1500 under a similar arrangement. By the mid-1500s, with the help of slave labor, the Portuguese settlers had turned the islands into Africa's foremost exporter of sugar. Sao Tome and Principe were taken over and administered by the Portuguese crown in 1522 and 1573, respectively.

Sugar cultivation declined over the next 100 years, and by the mid-1600s, Sao Tome was little more than a port of call for bunkering ships. In the early 1800s, two new cash crops, coffee and cocoa, were introduced. The rich volcanic soils proved well suited to the new cash crop industry, and soon extensive plantations (rocas), owned by Portuguese companies or absentee landlords, occupied almost all of the good farmland. By 1908, Sao Tome had become the world's largest producer of cocoa, still the country's most important crop.

The rocas system, which gave the plantation managers a high degree of authority, led to abuses against the African farm workers. Although Portugal officially abolished slavery in 1876, the practice of forced paid labor continued. In the early 1900s, an internationally publicized controversy arose over charges that Angolan contract workers were being subjected to forced labor and unsatisfactory working conditions. Sporadic labor unrest and dissatisfaction continued well into the 20th century, culminating in an outbreak of riots in 1953 in which several hundred African laborers were killed in a clash with their Portuguese rulers. This "Batepa Massacre" remains a major event in the colonial history of the islands, and the government officially observes its anniversary.

By the late 1950s, when other emerging nations across the African Continent were demanding independence, a small group of Sao Tomeans had formed the Movement for the Liberation of Sao Tome and Principe (MLSTP), which eventually established its base in nearby Gabon. Picking up momentum in the 1960s, events moved quickly after the overthrow of the Salazar and Caetano dictatorship in Portugal in April 1974. The new Portuguese regime was committed to the dissolution of its overseas colonies; in November 1974, their representatives met with the MLSTP in Algiers and worked out an agreement for the transfer of sovereignty. After a period of transitional government, Sao Tome and Principe achieved independence on July 12, 1975, choosing as its first president the MLSTP Secretary General, Manuel Pinto da Costa.

In 1990, Sao Tome became one of the first African countries to embrace democratic reform and changes to the constitution--the legalization of opposition political parties--led to elections in 1991 that were nonviolent, free, and transparent. Miguel Trovoada, a former prime minister who had been in exile since 1986, returned as an independent candidate and was elected president. Trovoada was re-elected in Sao Tome's second multiparty presidential election in 1996. The Party of Democratic Convergence (PCD) toppled the MLSTP to take a majority of seats in the National Assembly, with the MLSTP becoming an important and vocal minority party. Municipal elections followed in late 1992, in which the MLSTP came back to win a majority of seats on five of seven regional councils. In early legislative elections in October 1994, the MLSTP won a plurality of seats in the Assembly. It regained an outright majority of seats in the November 1998 elections. The Government of Sao Tome fully functions under a multiparty system. Presidential elections were held in July 2001. The candidate backed by the Independent Democratic Action Party, Fradique de Menezes, was elected in the first round and inaugurated on September 3. Parliamentary elections held in March 2002 led to a coalition government after no party gained a majority of seats.