Alphonse Nteziryayo was born in the commune of Kibayi in the Butare prefecture of Rwanda. He was Commander of the military police and Director of Civil Defence for the Butare prefecture. In this capacity he exercised authority over the Interahamwe militiamen (an extremist Hutu militia) and certain civilians in the prefecture. On 17 June 1994, he was appointed Préfet of Butare, a position he took over from Sylvain Nsabimana. He held this position until the beginning of July 1994, up until which date he fled Rwanda. In this capacity, he was the representative of the executive power at the prefecture level. He exercised his authority over his subordinates as well as over the different mayors of the prefecture, and was in a position to requisition the army and the national gendarmerie.
From the end of 1990 until July 1994, Nteziryayo was said to have adhered to, and participated in the detailed development of a plan aimed at exterminating the Tutsis. Amongst other elements, this plan included recourse to hatred and ethnic violence, the training of and distribution of arms to militias as well as the drafting of lists of people to be eliminated. In the accomplishment of this plan, he was accused of having planned, ordered and participated in the massacres. From April to July 1994, Nteziryayo was said to have publicly incited the population to exterminate the Tutsi population.
Between March and June 1994, Nteziryayo together with Joseph Kanyabashi (Mayor of Ngoma) allegedly helped and facilitated the military training of certain civilians in the communes of Ngoma and Nyakizu. Nteziryayo was also said to have incited the local population to massacre Tutsis in the Butare prefecture.
Before and during the 1994 killings in Butare, Nteziryayo reportedly distributed weapons to the militiamen and to certain civilians with the aim of exterminating the Tutsi population and the moderate Hutus.
In May and June 1994, Nteziryayo allegedly ordered the Interahamwe to search for Tutsis and to kill them.
Towards the middle of June 1994, Nteziryayo and Arsène Shalom Ntahobali (leader of a militia group) were both said to have tried to prevent the evacuation from Butare of around 300 orphans and the adults accompanying them. Overriding the opposition of the employees of the International Committee of the Red Cross and the local authorities, they allegedly selected about 40 adults who were forced to remain in Rwanda.
In early July, in the face of the advancing FPR (Front Patriotique Rwandais, an opposition group consisting mainly of Tutsi refugees and led by Paul Kagame), Nteziryayo fled Rwanda. On 24 April 1998, he was arrested in Burkina Faso.