Lying on the slopes of the Orontes valley, Antioch was encircled by walls studded by 400 towers. The river ran along the city's northern wall before entering Antioch from the northwest and exiting east through the northern half of the city. Mount Silpius, crested by a citadel, was the Antioch's highest point and rose some 1,000 feet (300 m) above the valley floor. There were six gates through which the city could be entered: three along the northern wall, and one on each of the south, east, and west sides. The valley slopes made approaching from the south, east, or west difficult, so the only way for an army to enter the Antioch was from the north across flatter ground. Muslim governor of the city, Yaghi-Siyan, was aware of the approaching crusader army as it marched through Anatolia in 1097; the city stood between the crusaders and Palestine. To prepare for crusaders arrival he imprisoned the Orthodox Patriarch of Antioch, John the Oxite, turned St Paul's Cathedral into a stable and expelled many leading Christians from the city; as well he began stockpiling supplies in anticipation of a siege.

Knowing they had to capture Antioch, the crusaders chose to advance on Antioch and establish a siege close to Antioch. On 20 October 1097 they reached a fortified crossing, known as Iron Bridge, on the Orontes River 12 miles (19 km) outside Antioch. The ensuing nine-month siege has been described as "one of the great sieges of the age". After stripping the surrounding area of food, the crusaders were forced to look farther afield for supplies, opening themselves to ambush and while searching for food on 31 December, a force of 20,000 crusaders encountered a relief force led by Duqaq of Damascus heading to Antioch and defeated the army. However, supplies dwindled and in early 1098 one in seven of the crusaders was dying from starvation and people began deserting in January.

At the end of May 1098 a Muslim army from Mosul under the command of Kerbogha approached Antioch. This army was much larger than the previous attempts to relieve the siege. The crusaders knew they would have to take the city before Kerbogha arrived if they had any chance of survival. Weeks earlier, Bohemund of Taranto, one of Crusade leaders, had secretly established contact with someone inside the city named Firouz, an Armenian guard who controlled the Tower of the Two Sisters. Firouz offered to let crusaders into the city in exchange for money and a title. On 2 June 1098 Firouz instructed Bohemund to feign a march south over the mountains to ostensibly confront Kerbogha, but then to double-back at night and scale the walls at the Tower of the Two Sisters where Firouz held watch. This was done. Firouz allowed a small contingent of Crusaders to scale the tower (including Bohemund), who then opened a nearby postern gate allowing a larger contingent of soldiers hiding in the nearby rocks to enter the city and overwhelm the alerted garrison.
The Antioch was taken.