He was born in Brooksby, Leicestershire, the son of the minor noble Sir George Villiers. As a youth he was noted for his beauty and he became a regular at the royal court in 1614 following his introduction to James during the king's progress of that year. Villiers gained support from those opposed to the current favourite, Robert Carr, Earl of Somerset and he was knighted in 1615 as a Gentleman of the Bedchamber. When Carr was disgraced after the Overbury affair his position was rapidly taken by Villiers, although the king's passion for Villiers had been obvious for some time before. He prospered greatly under the king, becoming an earl in 1617 and marquess in 1618.
He married the daughter of the Francis Manners 6th Earl of Rutland, Katherine Manners, later suo jure Baroness de Ros, on May 16, 1620 despite the objections of her father. Villiers was happy to grant valuable royal monopolies to her family. Parliament began an investigation into misuse of the monopolies in 1621 and Villiers was quick to side with Parliament to avoid action being taken against him.
In February 1623 he accompanied Prince Charles to Spain for marriage negotations regarding the Infanta Maria. The negotiations had long been stuck but it is believed that Villiers' crassness was key to the total collapse of agreement; the Spanish ambassador asked Parliament to have Villiers executed for his behaviour in Madrid. Despite this he was made a Duke in his absence and gained popularity by calling for war with Spain on his return. He headed further marriage negotiations but when in 1624 the betrothal to Henrietta Maria of France was announced the choice of a Catholic was widely condemned.
Villiers popularity suffered further when he was blamed for the failure of the von Mansfeld expedition to recover the Palatinate (1625). But when Charles became king Villiers was the only man to maintain his position from the court of James. When Parliament attempted to impeach him for the failure of the Cádiz expedition (1625) Charles had the house dissolved in August before they could put Villiers on trial.
In 1627 Villiers then led another failure to try and aid the Huguenots besieged at La Rochelle, losing over 4000 men out of a force of 7000. While organising a second attempt he was killed at Portsmouth by John Felton, a naval officer who held a personal grudge against him. Felton was hanged in November and Villiers was buried in Westminster Abbey.