Ndadaye was born in the town of Murama in Muramvya Province. He began studying as a teacher, but his education was interrupted by the massacres of 1972, whereupon he was forced to flee to Rwanda to avoid being killed. He took refuge in the southern Rwandan town of Butare and attended the Group Scolaire (school group). He finished his degree in education at the National University of Rwanda, and then completed a second degree in banking at the National Academy of Arts and Trades in France. He was a lecturer in Rwanda from 1980 to 1983. He worked as a banker thereafter, heading up a credit organisation from 1983 to 1988.
Ndadaye had become involved in politics while in Rwanda, serving as the inaugural president of the Mouvement des Étudiants Progressistes Barundi au Rwanda, a movement of exiled Burundian students from 1976 to 1979. He was involved in the foundation of the Burundi Workers' Party in 1979, and was actively involved in the party until his resignation in 1983 as a result of a dispute over party strategy. Ndadaye returned to Burundi in September of that year, by which time he was developing a political following of his own.
Ndadaye had been a key leader of the Burundi Workers' Party, and it subsequently fell into decline after his departure, ultimately being disbanded in the mid-1980s. Although opposition parties were banned in Burundi itself under the rule of military dictator Jean-Baptiste Bagaza, in 1986, Ndadaye and his supporters founded a new underground political movement, the moderate Front for Democracy in Burundi (FRODEBU). It remained underground until 1992, when Pierre Buyoya began a process of political liberalisation in advance of the country's first ever democratic elections and allowed the party to officially register.
The elections, held in June 1993, saw Ndadaye, endorsed by FRODEBU and three other predominately Hutu parties, the Rally for the People of Burundi (RPB), People's Party (PP), and the Liberal Party (PL), face up against the ruling Tutsi-dominated government under Buyoya. With the Hutu the dominant population in Burundi, Ndadaye won a crushing victory, receiving 65% of the vote to Buyoya's 32%. The poll was certified by international observers as being free and fair, and none of the candidates contested the poll. It was followed by success for his party in the legislative elections held later that month, winning 65 of 81 seats. After surviving a failed coup attempt on July 3, Ndadaye was sworn in as President of Burundi on July 10, 1993. The victory made him both the first democratically elected and first Hutu president of Burundi.
Ndadaye took a cautious, moderate approach as President, and attempted to resolve the deep ethnic divide in Burundian society. He named Sylvie Kinigi, a Tutsi, as the Prime Minister, and gave one third of the Cabinet posts and two regional governorships to Buyoya's Union for National Progress. He freed political prisoners, granted freedom of the press, granted amnesty to exiled former dictator Bagaza and moved slowly to address the entrenched disadvantage of the Hutus that had resulted from many years of minority Tutsi rule to avoid exacerbating tensions.
Despite his cautious approach to the presidency, some of his actions nevertheless provoked tensions in the community. He questioned contracts and concessions approved under previous Tutsi governments, which threatened the economics of the powerful Tutsi elite and army. He began reforms to the military, shifting the national police to a separate command and changing the admission requirements for the military and police so as to reduce the entrenched Tutsi dominance. The dominance of FRODEBU caused problems at a local level, as Ndadaye's Hutu supporters took over many positions previously held by Tutsis in the public service, and botched the resettlement of refugees returning after the 1972 massacres in such a way as to leave many Tutsi families homeless. The issues were exacerbated by the newly-free press, who began reporting in such a way as to inflame ethnic tensions.
Ndadaye's government was to be short-lived, however, as he was overthrown and killed in a military coup on October 21. The exact events have never been clarified, but it appears that Ndadaye, Pontien Karibwami, the president of the National Assembly and Gilles Bimazubute, the vice-president of the National Assembly, were taken to an army barracks before dawn by supposedly loyal soldiers under the guise that there had been a mutiny by sections of the army and that they needed protection. The three, along with a number of other officials and cabinet members, were then executed, with Ndadaye bayonetted to death.
Ndadaye's death sparked severe ramifications across the country. The attempted coup rapidly failed, as Francois Ngeze, the civilian politician installed as temporary head of state, refused to support the coup leaders and called for Prime Minister Kinigi, who had survived the coup and was in hiding at the French embassy to assume control, a move soon backed by key military chiefs. Kinigi was thus appointed as acting president while a resolution to the constitutional crisis caused by the assassination of both the president and the president of the assembly was found. The United Nations Security Council condemned the assassination and coup, and was soon followed in doing so by the United Nations General Assembly. Many thousands of civilians, on both sides, were killed in the resulting carnage, with estimates varying but generally agreed to be above 100,000. The ongoing violence developed into the decade-long Burundi Civil War.
A United Nations investigation into Ndadaye's murder, the result of which was released in 1996, accused the army command of being responsible for the assassination and of being complicit in the resulting massacres by Tutsi troops. It did not name specific figures as being responsible, but Buyoya, Ndadaye's predecessor as president, has long been suspected of having some role in the assassination.
In 1999, as part of attempts to end the civil war, an array of arrests were made of those suspected of involvement in the Ndadaye assassination. Five men, including the alleged ringleader, army officer Paul Kamana, were sentenced to death, and 74 others received sentences ranging from one year to twenty years. Most of the high-ranking officials charged, however, were acquitted, in a verdict condemned by Ndadaye's supporters.