The November 15 attacks were timed to coincide with the Sabbath morning, when synagogues would be occupied. At the Bet Israel Synagogue on Nakiye Elgün Street in Şişli, the truck detonated at approximately 9:30 a.m. local time. Search-and-rescue teams pulled survivors from the debris of surrounding buildings. Four minutes later, at 9:34 a.m., the second bomb exploded at the Neve Shalom Synagogue in Beyoğlu, a congregation that had already survived an attack in 1986, when 22 people were killed. The six Jewish victims of the November 15 attack — Yoel Ülçer Kohen, Berta Özdoğan, Yona Romano, Annette Rubinstein, Anna Rubinstein, and Avram Varol — were buried at the Ulus Ashkenazi Jewish Cemetery. They were laid to rest in the front section of the mausoleum where the 1986 victims already lay.

An initial claim of responsibility came from IBDA-C, a Turkish Islamist militant group. Investigators later determined the attacks had been orchestrated by al-Qaeda.

On November 20, as US President George W. Bush was in London meeting with Prime Minister Tony Blair, two more truck bombs struck. The timing appeared deliberate: investigators later concluded the attackers may have planned the second wave to coincide with the high-profile Anglo-American summit.

At approximately 10:55 a.m., a truck carrying roughly 700 kilograms of ammonium sulfate, ammonium nitrate, and compressed fuel oil detonated at the HSBC General Headquarters in Beşiktaş. The explosion made the first six above-ground floors unusable and badly damaged the building's facade. The bombers had waited for a red traffic light to maximize the blast's effect on those in the street. Minutes later, at 11:00 a.m., a second truck drove through the security entrance of the British Consulate on Meşrutiyet Avenue in Beyoğlu and detonated. The outer wall of the consulate's front garden collapsed onto passing cars. A fire burned inside. Among the dead was the British Consul-General Roger Short. Thirty-one people were killed in the second round of attacks, and more than 450 were wounded.

Among those who died at the HSBC building was Turkish actor and singer Kerem Yılmazer, who had been heading to the nearby NTV building where he worked as a voice actor. His wife, actress Göksel Kortay, was on a live program at another network when news of the bombing broke.

In total, 59 people died in the four bombings — including the four suicide bombers — and more than 750 were wounded. The death count rose incrementally in the days and weeks that followed, as victims succumbed to injuries in hospital. Celal Dilsiz, who had survived the initial blasts, died on February 9, 2004, nearly three months later, bringing the confirmed toll to its final figure.

The physical damage extended well beyond the four primary targets. Istanbul Governor Muammer Güler reported that 58 buildings in Beyoğlu had been inspected after the synagogue attacks, of which nine were severely damaged and three moderately damaged, representing approximately 25 million US dollars in losses. In Şişli, 52 buildings were examined. The Beyoğlu district mayor reported that 38 buildings, 25 of them considered historic, had been damaged. Istanbul's Jewish community, already living with the memory of 1986, faced the accumulated weight of two generations of targeted violence.

Turkish authorities charged 74 people in connection with the bombings. Investigations determined that al-Qaeda had orchestrated the attacks. Harun Ilhan, one of the central suspects, admitted involvement and identified himself as 'an al-Qaeda warrior.' Habib Akdaş, another alleged ringleader, fled to Iraq, where he was reportedly killed by coalition forces in Fallujah. Syrian national Loai al-Saqa had already faced terrorism charges in Jordan.

On February 16, 2007, al-Saqa and Ilhan were convicted and sentenced to 67 consecutive life sentences — one for each of the victims, plus additional terms for terrorism and conspiracy. Five other men were convicted for their organizing roles. Forty-nine defendants in total were sentenced to various terms of imprisonment, and 26 were acquitted.