Through her mother, she was a descendant of king David I of Scotland. Born in or around 1210, she was a granddaughter of Maud of Chester, and of David of Scotland, 8th Earl of Huntingdon, himself the youngest brother to two Kings of Scotland, Malcolm IV and William the Lion, Dervorguilla's mother Margaret being the couple's eldest daughter.
As her father died in 1234 without a legitimate son (he had an illegitimate son named Thomas), according to both Anglo-Norman feudal laws and to ancient Gaelic customs, she was one of his heiresses, her two sisters Helen and Christina being older and therefore senior. This might be considered an unusual practice in England, but it was more common in Scotland and in Western feudal tradition. Because of this, Dervorguilla bequeathed lands in Galloway to her descendants, the Baliol and the Comyns. Dervorguilla's son John of Scotland was briefly a King of Scots too, known as Toom Tabard (Scots: 'puppet king' literally "empty coat").
In 1263, her husband Sir John was required to make penance after a land dispute with Walter Kirkham, Bishop of Durham. Part of this took the very expensive form of founding a College for the poor at the University of Oxford. Sir John's own finances were less substantial than those of his wife, however, and long after his death it fell to Dervorguilla to confirm the foundation, with the blessing of the same Bishop as well as the University hierarchy. She established a permanent endowment for the College in 1282, as well as a Code of Statutes which still (ostensibly) governs the College now. The college still retains the name Balliol College, and its main historical society, the Dervorguilla society.
When Sir John died in 1269, Dervorguilla had his heart embalmed and kept in a casket of ivory bound with silver. The casket travelled with her for the rest of her life.
In her last years, the main line of the royal House of Scotland was threatened by a lack of male heirs, and Dervorguilla, who died just before the young heiress Margaret, the Maid of Norway might, if she had outlived her, have been one of the claimants to her throne. Devorguilla was buried beside her husband at Dumfries Abbey, which was christened 'Sweetheart Abbey', the name which it retains to this day. The depredations suffered by the Abbey in subsequent periods have caused both the graves to be lost.
Owing to the deaths of her elder two sons, both of whom were childless, Dervorguilla's third and youngest surviving son John of Scotland asserted a claim to the crown in 1290 when queen Margaret died. He won in arbitration against the rival Robert Bruce, 5th Lord of Annandale in 1292, and subsequently was king of Scotland for four years (1292-96).