In May 1306 Hugh le Despenser the younger was knighted, and that summer he married Eleanor de Clare, daughter of Gilbert de Clare, 9th Lord of Clare and 7th Earl of Hertford and Joan of Acre.
Eleanor was the niece of the new king, Edward II of England, and this connection brought Despenser closer to the English royal court. He joined the baronial opposition to Piers Gaveston, the king's favourite (and Hugh's brother-in-law, as Gaveston was married to Eleanor's sister Margaret).
Hugh le Despenser the younger became royal chamberlain in 1318. As a royal courtier, Despenser manoeuvred into the affections of King Edward, displacing the previous favourite, Roger d'Amory.
Finally the barons prevailed upon King Edward and forced Despenser and his father into exile in August 1321. Following the exile of the Despensers, the barons who opposed them fell out among themselves, and the King summoned the two men back to England. Early in the following year, King Edward took advantage of these divisions to secure the surrender of Marcher Lord Roger Mortimer, and the defeat and execution of the Earl of Lancaster, the Despensers' chief opponents. The pair returned and King Edward quickly reinstated Despenser as royal favourite.
Queen Isabella had a special dislike for Hugh le Despenser the younger. Alison Weir, in her 2005 book Queen Isabella: Treachery, Adultery, and Murder in Medieval England, speculates that he had raped Isabella and that was the source of her hatred. While Isabella was in France to negotiate between her husband and the French king, she formed a liaison with Roger Mortimer and began planning an invasion. Despenser supposedly tried to bribe French courtiers to assassinate Isabella, sending barrels of silver as payment. Roger Mortimer and the Queen invaded England in October 1326. Their forces numbered only about 1,500 mercenaries to begin with, but the majority of the nobility rallied to them throughout October and November. By contrast, very few people were prepared to fight for Edward II, mainly because of the hatred that the Despensers had aroused. The Despensers fled West with the King, with a sizeable sum from the treasury. The escape was unsuccessful. Separated from the elder Despenser, the King and the younger Despenser were deserted by most of their followers, and were captured near Neath in mid-November. King Edward was placed in captivity and later forced to abdicate in favour of his son. The elder Despenser (the father) was hanged at Bristol on 27 October 1326, and younger Despenser (the son) was brought to trial.
Hugh le Despenser the younger tried to starve himself before his trial, but he did face trial on 24 November 1326, in Hereford, before Mortimer and the Queen. Despenser was then tied to a ladder, and —in full view of the crowd— had his genitals sliced off and burned (in his still-conscious sight) then his entrails slowly pulled out, and, finally, his heart cut out and thrown into the fire. Finally, his corpse was beheaded, his body cut into four pieces, and his head mounted on the gates of London. Mortimer and Isabella feasted with their chief supporters, as they watched the execution.