The area that became Portuguese Guinea was first visited by the Portuguese in 1446–47, and in the 16th cent. it was an important source of slaves sent to South America. The territory was administered as part of the Portuguese Cape Verde Islands possession until 1879, when it became a separate colony. In 1951 it was constituted an overseas province.

In 1956, Amilcar Cabral founded the African Party for the Independence of Guinea and Cape Verde (PAIGC). After some years of sporadic violence, the PAIGC launched a war of independence in Portuguese Guinea in the early 1960s; in 1973 it declared the province, renamed Guinea-Bissau, independent of Portugal. A government was established and elections for a national assembly were held in PAIGC-controlled areas. Following the coup in Portugal (1974), the new Portuguese government initiated negotiations with the PAIGC.

In Aug., 1974, an agreement was reached under which Portugal granted (Sept. 10) independence to Guinea-Bissau. Luis de Almeida Cabral (the brother of Amilcar Cabral, who had been assassinated in 1973) became the first president, and Guinea-Bissau was admitted to the United Nations that year. Although Portugal refused to give the Cape Verde Islands and Guinea-Bissau independence together (granting Cape Verde separate independence in 1975), the two maintained the PAIGC as a common political party for five years. Guinea-Bissau remained a single-party state with limited civil rights. Security was a primary concern in the early years of independence, as the regime was weak in Bissau where there was lingering support for the Portuguese.

In 1980 a coup brought João Bernardo Vieira to power. The new regime opposed unification with Cape Verde, but relations between the two nations were normalized in 1983. Although Vieira's regime in the 1980s was characterized by purgings of political enemies and suppression of dissent, he also introduced health reforms and initiatives to increase agricultural production and economic diversity. However, the economy did poorly and the country relied on outside aid to make up for enormous deficits. In 1991 the national assembly officially revoked the PAIGC's status as the sole legal party, and in 1994 Vieira was chosen as president in the country's first free elections.

An army mutiny began in June, 1998, eventually turning into a war in which neighboring Senegal and Guinea intervened on Vieira's behalf, but the coup almost marked the beginning of a period of economic and political troubles. In May, 1999, the military ousted Vieira and installed Malam Bacai Sanhá, the former head of parliament, as interim president. In Dec., 1999, two opposition parties won a majority in parliament, and, after defeating Sanhá in a runoff in Jan., 2000, Party for Social Renewal (PRS) candidate Kumba Yala won the presidency. An army rebellion in Nov., 2000, by former junta leader Gen. Ansumane Mane was crushed and Mane was killed. Yala, hampered by the poor economy and heading an unstable government, was ousted in Sept., 2003, by a military coup that subsequently received the support of many civilian leaders. Businessman Henrique Rosa was appointed president of a transitional national government. Parliamentary elections in Mar., 2004, resulted in a plurality for the PAIGC, and Carlos Gomes, Jr., became prime minister with the support of the PRS. In October the chief of the armed forces was killed in a brief mutiny over back pay, but a peaceful end to uprising was negotiated.

Presidential elections were held in June, 2005, and were dominated by the candidacies of former presidents Vieira (who returned from exile), Sanhá, and Yala (who had originally been barred from political activity but was nominated by the PRS and was permitted to run). The month before the election Yala claimed to be the rightful president, revoking his renunciation of power and occupying the presidential palace. Although Yala's move came to nothing, it raised tensions in the nation. When he placed third in the June vote Yala claimed to have won nonetheless, but ended up accepting the results even as he denied them. A runoff between Sanhá, who placed first but failed to win a majority, and Vieira in July resulted in a win for Vieira. Sanhá asserted the vote was marred by fraud, and his party, the PAIGC, refused until September to recognize the result.

At the end of Oct., 2005, Vieira dismissed Gomes as prime minister, and then appointed Aristides Gomes, a political ally, to the post. In Mar., 2006, fighting erupted when government troops attempted to oust Casamance rebels from Senegal who had established bases in NW Guinea-Bissau. A no-confidence vote in Gomes's goverment in Mar., 2007, led to the appointment of Martinho N'Dafa Cabi, a PAIGC leader, to the post the next month. In July, 2007, the president, citing the nation's financial straits, rescheduled the Mar., 2008, parliamentary elections so that they would coincide with the 2009 presidential election.

When Prime Minister Cabi dismissed several officials in July, 2008, without consulting the coalition parties, the PAIGC withdrew from the government; the president subsequently dissolved parliament and the cabinet and called for new elections in November. In August, Carlos Correia was named prime minister. Also that month, an attempted coup by the head of the navy, Rear Admiral José Américo Bubo Na Tchuto, was foiled. The parliamentary elections were won by the PAIGC, and in Jan., 2009, Carlos Gomes, Jr., again became prime minster.

Meanwhile, in Nov., 2008, there was another apparent coup attempt against the president; the armed forces chief of staff had, during the elections, accused the president of being involved with drug traffickers. In Jan., 2009, the president's guard was blamed for an assassination attempt against the armed forces chief, who subsequently was killed in an explosion in March. Vieira was assassinated the next day by soldiers who blamed him for the bombing, and parliament speaker Raimundo Pereira became interim president. The military subsequently continued a campaign of violence against perceived opponents. In April a former prime minister who had criticized the military was severely beaten by soldiers, and in June a presidential candidate and a former defense minister were killed (and subsequently accused of plotting a coup).

In the presidential election in late June, PAIGC candidate Malam Bacai Sanhá came in first but won only a plurality of the vote, necessitating a runoff with Kumba Yala in July, which Sanhá won. Yet another apparent coup attempt occurred in Apr., 2010, apparently by supporters of Rear Admiral Na Tchuto, who had returned to the country and found refuge in the UN's local headquarters in Dec., 2009; the government had been seeking his surrender. Though the government was not overthrown, real power in Guinea-Bissau appeared to shift to the military, in particular to Na Tchuto, who was subsequently accused by the U.S. government of drug trafficking. A possible coup attempt in Nov., 2011, led to the arrest of Na Tchuto and the former head of the army.

In Jan., 2012, President Sanha died abroad while in Paris for medical treatment; parliament speaker Raimundo Pereira became interim president. A coup in April was apparently sparked by the expected election of Carlos Gomes, Jr., as president in a runoff vote. The army was known not to favor Gomes, and his opponent, former president Yala, had lost badly in the first round and alleged the election had been rigged. In May, a transitional government was established with Manuel Serifo Nhamadjo, a former president of the assembly, as president, and Rui Duarte de Barros as prime minister; one of the coup leaders became defense minister, and West African forces were deployed in Guinea-Bissau as peacekeepers. Na Tchuto was released from prison in June.

According to the UN and other international officials, the flow of illegal drugs through the country increased after the coup. In Oct., 2012, an apparent coup attempt failed; the government accused Gomes, Portugal, and other Portuguese-speaking nations of being behind it. In Apr., 2013, Na Tchuto was arrested in international waters by U.S. drug agents in a drugs-for-weapons sting operation, and a year later pleaded guilty in the United States to drug-importation charges. Gen. Antonio Indjai, the armed forces chief, was later indicted by the United States on trafficking charges arising from the same case.

The 2014 presidential election, decided after a runoff in May, resulted in a win for José Mário Vaz, a former finance minister and the PAIGC candidate, and the PAIGC's Domingos Simões Pereira was subsequently (July) appointed prime minister. In August, Indjai was dismissed as armed forces chief. Tensions between the president and prime minister led to the dismissal of Pereira's government in Aug., 2015. A new government was not formed until October; the PAIGC's Carlos Correia became prime minister.

Conflicts within the PAIGC led to some loss of support for the government in the assembly, however, and in May, 2016, Vaz dismissed Correia's cabinet and called upon the PAIGC to form a new government. Vaz subsequently named Baciro Djá prime minister by decree, but in November he dismissed Djá's government under an October agreement brokered by the Economic Community of West African States (ECOWAS), which was designed to end the conflict in the PAIGC and instability in the government since Pereira's dismissal and to lead to the appointment of a consensus prime minister. Former general Umaro Sissoco Embaló was then named prime minister, but he had not been agreed to by the PAIGC, and the political crisis continued.

In Jan., 2018, Vaz named Augusto Antonio Artur da Silva to succeed Siccoco, but da Silva also had not been selected through consensus. In February ECOWAS imposed sanctions on Vaz's political and business associates, and in April, after a summit in Togo, Vaz appointed Aristides Gomes as prime minister. Parliamentary elections in Mar., 2019, resulted in a sizable plurality for the PAIGC, and Vaz again blocked Pereira from becoming prime minister; in June Gomes again was named prime minister.

After Vaz's term ended in June, and with the presidential election not slated till November, legislators voted to name assembly speaker Cipriano Cassamá interim president, but after mediation by ECOWAS, Vaz became interim president but no longer managed government affairs. In October Vaz sought unsuccessfully to replace Gomes. In the presidential election, opposition candidate and former prime minister Embaló won after a December runoff, defeating the PAIGC's Pereira, who challenged the result in court; Vaz was eliminated in the first round. After Embaló, who had the support of the military, was sworn in in Feb., 2020, he appointed Nuno Gomes Nabiam as prime minister. PAIGC legislators then elected Cassamá interim president, but he resigned a few days later.

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