Güyük received military training and served as an officer under Genghis and Ögedei. In 1233, he conquered the short-lived Dongxia Kingdom of Puxian Wannu.
He participated in the invasion of Russia and eastern Europe in 1236-1241 with other Mongol princes, including his cousin . During the course of the invasion, Güyük quarreled violently with Batu and was recalled for a time to Mongolia. This breach between the families of and , the first and third sons of Genghis Kahn, would widen over time and prove the ultimate downfall of the Mongol Empire.
In the meantime Ögedei had died in 1241, and his widow T& had taken over as regent, a position of great influence and authority which she used to advocate for her son Güyük. Batu withdrew from Europe so that he might have some influence over the succession, but despite his delaying tactics, Töregene succeeded in getting Güyük elected in 1246.
Guyuk's enthronement on 24 August 1246, near the Mongol capital at Karakorum, was attended by a large number of foreign ambassadors: the Franciscan friar and envoy of Pope Innocent IV, ; the Grand Duke of Moscow Yaroslav II of Vladimir; the incumbents for the throne of ; the brother of the king of and historian, Sempad the Constable; the future , Kilij Arslan IV; and ambassadors of the Abbasid Caliphate and of the emperor of India. According to John of Plano Carpini, Güyük's formal election in a great ''kurultai'', or diet of the tribes, took place while his company was at a camp called ''Sira Orda'', or "Yellow Pavilian," along with 3,000 to 4,000 visitors from all parts of Asia and eastern Europe, bearing homage, tribute, and presents. They afterwards witnessed the formal enthronement at another camp in the vicinity called the "Golden Ordu," after which they were presented to the emperor.
Güyük reversed several unpopular edicts of his mother the regent and made a surprisingly capable khan, appointing Eljigidei in Persia in preparation for an attack on Baghdad and pursuing the war against the Song Dynasty. He was, nevertheless, insecure and won the disapproval of his subjects by executing several high-ranking officials of the previous regime for treason. Although Batu did not support Guyuk's election seriously, he expected the Great Khan as tradionalist and sent Andrey and Alexander Nevsky to Karakorum in Mongolia in 1247 after their father's death. Guyuk appointed Andrey Grand Duke of Vladimir and Alexander prince of Kiev.
In 1248, he demanded Batu come towards Mongolia to meet him, a move that some contemporaries regarded as a pretext for Batu's arrest. In compliance with the order, Batu approached bringing a large army. Güyük prepared for battle, and civil war seemed imminent.
The showdown never happened— Güyük died in route, in what is now Xinjiang; he had succumbed at about the age of forty-two to the combined effects of alcoholism and gout. His widow Oghul Qaimish took over as regent, but she would be unable to keep the succession within her branch of the family. M& succeeded as Khan in 1251.
Genghis Khan's sons and grandsons, were haunted by alcoholism, a vice that Genghis himself had detested. Despite this, Genghis himself once remarked that it was not realistic to expect a man not to get drunk on occasion. The death of Güyük had a profound effect on history. Güyük wanted to turn the Mongol power against Europe. Because of Güyük's premature death, Mongol family politics caused the Mongol efforts to be directed against southern China, which was eventually conquered in the time of Kublai Khan.
Güyük's reign showed that the split between Batu's line, the descendants of Jöchi, and the rest of the family was the fatal flaw in the unity of all the Mongol Empire. The civil war which split the empire into rival khanates might well have occurred in Güyük's time had he not died early. Batu eventually backed Möngke and helped to establish him as Great Khan, thereby replacing the house of Ögodei with that of Tolui.
Oghul Qaimish, whom Möngke had called "more contemptible than a bitch" to a European visitor, was executed after Batu and Möngke affected the family coup.