The explosion tore through the chapel adjacent to the cathedral's main entrance. Initial reports were confused -- authorities could not immediately determine whether the device had been planted in advance or carried in by a bomber. The scale of destruction suggested a large device either way. An unnamed church source told Nile TV the bomb had been thrown inside the cathedral's hall. St. Mark's Cathedral is normally under constant security patrol, and the Interior Ministry opened an investigation into the police unit assigned to the church complex. Among the dead were women, children, and elderly worshippers who had come for a routine Sunday service. Their names joined a long and painful list of Coptic victims of sectarian violence in Egypt.

President Abdel Fattah el-Sisi identified the bomber the following day as Mahmoud Shafiq Mohammed Mustafa. Three men and a woman were arrested in connection with the attack, with two more suspects sought. On 13 December, the Islamic State of Iraq and the Levant claimed responsibility through its Amaq News Agency. The Egyptian Interior Ministry's investigation pointed to a cell led by Mohab Mostafa El-Sayed Kassem, which the ministry linked to Ansar Bait al-Maqdis -- also known as ISIL's Sinai Province. The ministry further alleged that Muslim Brotherhood fugitives in Qatar had provided financing and logistical support, a claim both the Brotherhood and the Qatari government denied. By early 2017, eight suspects had been arrested. The bomber himself had been detained once before, in 2014 in Faiyum province, on charges of Brotherhood membership.

President Sisi declared three days of national mourning, calling the attack evidence of "vicious terrorism waged against the country's Copts and Muslims." Coptic Pope Tawadros II, who cut short a trip to Greece to return to Cairo, framed the bombing as "not just a disaster for the Church but a disaster for the whole nation." On 12 December, Sisi and Tawadros led the funeral procession together, a public display of solidarity that carried weight in a country where sectarian tensions run deep. Bishop Youssef of the Coptic Orthodox Diocese of the Southern United States urged fasting and prayer "not for the martyrs" but for the healing of the Egyptian people and for Muslims and Christians to live peacefully together. Egypt's Army Corps of Engineers began immediate restoration work, aiming to have the chapel ready for the Coptic Nativity celebration on 7 January.

The Botroseya bombing did not occur in isolation. It followed the 2011 Alexandria church bombing, which killed 23 people on New Year's Eve, and preceded the 2017 Palm Sunday attacks on churches in Tanta and Alexandria that killed 45. For Egypt's Coptic Christians -- a community that predates Islam in Egypt by centuries -- the pattern of attacks against churches, monasteries, and worshippers represents an existential threat that security forces have struggled to contain. The international response to the Botroseya bombing was broad: the UN Security Council condemned the attack, Pope Francis expressed personal solidarity with Tawadros, and governments from Algeria to the Philippines issued statements of condemnation. Egyptian academic Azza Radwan Sedky published an open letter to the bomber in Ahram Online, writing: "Your kind will never be able to command any country in the world because every country and every human being wishes you ill." The chapel was rebuilt. The scars on the community run deeper.