The siege of Antioch took place during the First Crusade in 1097 and 1098, on the crusaders' way to Jerusalem through Syria. Two sieges took place in succession. The first siege, by the crusaders against the city held by the Seljuk Empire, lasted from 20 October 1097 to 3 June 1098. The second siege, of the crusader-held city by a Seljuk relieving army, lasted three weeks in June 1098, leading to the Battle of Antioch in which the crusaders defeated the relieving army led by Kerbogha. The crusaders then established the Principality of Antioch, ruled by Bohemond of Taranto.Antioch (modern Antakya) lay in a strategic location on the crusaders' route to Palestine through the Syrian Coastal mountain range. Supplies, reinforcements and retreat could all be controlled by the city. Anticipating that it would be attacked, the Seljuk governor of the city, Yasyan, began stockpiling food and sending requests for help. The Byzantine walls surrounding the city presented a formidable obstacle to its capture, but the leaders of the crusade felt compelled to besiege Antioch anyway.

The crusaders arrived outside the city on 21 October and began the siege. The garrison sortied unsuccessfully on 29 December. After stripping the surrounding area of food, the crusaders were forced to look farther afield for supplies, opening themselves to ambush. On 31 December, a force of 20,000 crusaders encountered a relief army led by Duqaq, ruler of Damascus, heading to Antioch and defeated them. As the siege went on, supplies dwindled and in early 1098 one in seven of the crusaders was dying from starvation, and people began deserting.

A second relief force, this time under the command of Duqaq's brother Ridwan, emir of Aleppo, advanced towards Antioch, arriving on 9 February. Like the army of Duqaq before, it was defeated. Antioch was captured on 3 June, although the citadel remained in the hands of the Muslim defenders. Kerbogha, atabeg of Mosul, began the second siege, against the crusaders who had occupied Antioch, which lasted from 7 to 28 June 1098. The second siege ended when the crusaders exited the city to engage Kerbogha's army in battle and succeeded in defeating them. On seeing the Muslim army routed, the defenders remaining in the citadel surrendered.

The First Crusade (1096–1099) was the first of a series of religious wars, or Crusades, initiated, supported and at times directed by the Latin Church in the medieval period. The objective was the recovery of the Holy Land from Islamic rule. While Jerusalem had been under Muslim rule for hundreds of years, by the 11th century the Seljuk takeover of the region threatened local Christian populations, pilgrimages from the West, and the Byzantine Empire itself. The earliest initiative for the First Crusade began in 1095 when Byzantine emperor Alexios I Komnenos requested military support from the Council of Piacenza in the empire's conflict with the Seljuk-led Turks. This was followed later in the year by the Council of Clermont, during which Pope Urban II supported the Byzantine request for military assistance and also urged faithful Christians to undertake an armed pilgrimage to Jerusalem.

This call was met with an enthusiastic popular response across all social classes in western Europe. Mobs of predominantly poor Christians numbering in the thousands, led by Peter the Hermit, a French priest, were the first to respond. What has become known as the People's Crusade passed through Germany and indulged in wide-ranging anti-Jewish activities, including the Rhineland massacres. On leaving Byzantine-controlled territory in Anatolia, they were annihilated in a Turkish ambush led by the Seljuk Kilij Arslan at the Battle of Civetot in October 1096.

In what has become known as the Princes' Crusade, members of the high nobility and their followers embarked in late-summer 1096 and arrived at Constantinople between November and April the following year. This was a large feudal host led by notable Western European princes: southern French forces under Raymond IV of Toulouse and Adhemar of Le Puy; men from Upper and Lower Lorraine led by Godfrey of Bouillon and his brother Baldwin of Boulogne; Italo-Norman forces led by Bohemond of Taranto and his nephew Tancred; as well as various contingents consisting of northern French and Flemish forces under Robert Curthose (Robert II of Normandy), Stephen of Blois, Hugh of Vermandois, and Robert II of Flanders. In total and including non-combatants, the forces are estimated to have numbered as many as 100,000.

The crusaders marched into Anatolia. With Kilij Arslan absent, a Frankish attack and Byzantine naval assault during the Siege of Nicea in June 1097 resulted in an initial victory for the crusaders. In July, the crusaders won the Battle of Dorylaeum, fighting Turkish lightly-armoured mounted archers. Next the crusaders marched through Anatolia, suffering casualties from starvation, thirst, and disease. The decisive and bloody Siege of Antioch was fought beginning in 1097 and the city was captured by the crusaders in June 1098. Jerusalem was reached in June 1099 and the Siege of Jerusalem resulted in the city being taken by assault from 7 June to 15 July 1099, during which its defenders were ruthlessly massacred. The Kingdom of Jerusalem was established as a secular state under the rule of Godfrey of Bouillon, who shunned the title of "king". A counterattack was repulsed that year at the Battle of Ascalon, ending the First Crusade. Afterwards the majority of the crusaders returned home.

Four Crusader states were established in the Holy Land: the Kingdom of Jerusalem, the County of Edessa, the Principality of Antioch, and the County of Tripoli. The Crusader presence remained in the region in some form until the loss of the last major Crusader stronghold in the Siege of Acre in 1291. After this loss of all Crusader territory in the Levant, there were no further substantive attempts to recover the Holy Land.