Bohemond VI was the son of Bohemond V of Antioch and Luciana (Lucienne) di Caccamo-Segni, great-niece of Pope Innocent III. When Bohemond V died in January 1252, 15-year-old Bohemond VI succeeded under the regency of his mother. However, Luciana never left Tripoli, and instead handed over the government of the principality to her relatives. This made her unpopular, so the young Bohemond VI, through the approval of King Louis IX of France, who was on Crusade at the time, gained permission from Pope Innocent IV to inherit the principality a few months early. Young Bohemond then travelled to Acre where he was knighted by King Louis, and took power in Antioch. Through the efforts of King Louis, a truce was also negotiated between Antioch and Cilician Armenia. At Louis's suggestion, in 1254 the 17-year-old Bohemond married Sibylla of Armenia, daughter of Hetoum I of Armenia, which ended the power struggle between the two states that had been started by Bohemond IV, his grandfather.
Bertrand's son Bartholomew Embriaco became mayor of a Commune set up by the Embriaco family. Bartholomew's brother William, along with his cousin the lord of Gibelet, were eventually defeated by Bohemond's son, Bohemond VII, and then completely driven out by the Muslims.
The Mongols rewarded Bohemond for his allegiance, and returned to him various areas that had been lost to the Muslims, such as Lattakieh, Darkush, Kafar-dubbin, Laodicea, and Jabala. Bohemond was then able to re-occupy them, with the assistance of some Templars and Hospitallers.
In return for the lands, Bohemond had to install the Greek patriarch Euthymius at Antioch, in place of the Latin patriarch, since the Mongols were trying to strengthen ties with the Byzantine Empire. This earned Bohemond the enmity of the Latins at Acre, and Bohemond was excommunicated by the Patriarch of Jerusalem, Jacques Pantaléon. Pope Alexander IV put Bohemond's case on the agenda of his upcoming council (as well as the cases of Hetoum I of Armenia, and Daniel of Russia), but died in 1261, just months before the Council could be convened. For a new Pope, the choice fell to Pantaléon, who took the name Pope Urban IV, and after hearing Bohemond's explanation for his submission to the Mongols, suspended his excommunication sentence.
After taking Damascus, the Mongol Army had to cease their westward push, due to internal troubles in the Mongol Empire. The bulk of the Mongol army left Syria, with a smaller force left under Kitbuqa to occupy the territory. This provided an opportunity for the Egyptian Mamluks. The Mamluks advanced northward from Cairo to engage the Mongols, along the way negotiating an unusual pact of neutrality with the Franks of Acre that allowed the Egyptians to pass through Frankish territory unmolested. The Mamluks were thereby able to defeat the Mongols at the historic Battle of Ain Jalut in September 1260. With the Mongol army removed, the Mamluks then proceeded to conquer Syria and Iran, which had been previously ravaged by the Mongols. The Mamluks, under their leader Baibars, also began to threaten Antioch.
In 1263, Bohemond and Hethoum tried various methods of regaining control of the situation. They kidnapped the Greek patriarch Euthymius, and carried him off to Armenia, replacing him with the Latin Opizon. They also attempted to gain some financial leverage over the Mamluks. For example, Bohemond and Hethoum controlled the forests of southern Anatolia and Lebanon, the wood of which was needed by the Egyptian Mamluks to build ships. Hethoum attempted to use this as a bargaining chip to obtain a truce with the Mamluks. However, the attempts at blockade merely further incited Baibars.
In 1264, Bohemond also sought assistance from the Mongols. He traveled to the court of Hulagu, trying to obtain as much support as possible from the Mongol rulers against the Mamluk progression. However, Hulagu was unhappy with Bohemond for replacing the Greek patriarch with a Latin one, as the Byzantine alliance was important to him, against the Turks in Anatolia.
Baibars was angry at his generals' weakness, and returned to the attack. In May 1267 he attacked Acre, and in 1268 he began the Siege of Antioch, taking the city while Bohemond was away in Tripoli. All of northern Syria was quickly lost, leaving Bohemond with no estates except Tripoli.
Baibars attacked again in 1271 by starting the Siege of Tripoli, sending a letter to Bohemond threatening him with total annihilation and taunting him for his alliance with the Mongols:
Bohemond begged for a truce, so as not to lose Tripoli as well. Baibars mocked him for lack of courage, and asked him to pay all the expenses of the Mamluk campaign. Bohemond had enough pride left to refuse the offer, but in May Baibars offered him a truce anyway. By this time, the Mamluks had captured every inland castle of the Franks, but the Mamluks had heard reports about a new Crusade, this one from the prince who would later be Edward I of England. Edward had landed in Acre on May 9, 1271, where he was soon joined by Bohemond and his cousin King Hugh of Cyprus and Jerusalem.
Bohemond died in 1275, leaving a son and three daughters: Bohemond VII, nominal prince of Antioch (though Antioch had ceased to exist) and count of Tripoli; Isabeau de Poitiers, who died unmarried and without issue; Lucia, countess of Tripoli, later titular countess of Tripoli; and Marie de Poitiers (d. ca 1280), married to Nicolas de Saint-Omer (d. 1294).
The rancour of the Mamluks regarding Bohemond VI's alliance with the Mongols would remain until 1289 with the final Fall of Tripoli.