He was the eldest son of Thomas Sackville, 1st Earl of Dorset, by Cecily, daughter of Sir John Baker.
He was admitted to the Inner Temple in 1580 but not called to the bar, and was elected to the House of Commons in 1585 as member for Sussex, aged 23, by his father's influence.
He inherited from his father manors in Sussex, Essex, Kent, and Middlesex, the principal seats being Knole and Buckhurst.
His wife's family had fallen into disgrace in 1572 following the involvement of her father, the 4th Duke of Norfolk, in Ridolfi plot to overthrow Elizabeth I, install Mary I Stuart, Queen of Scots on the English throne and restore Catholicism in England.
In 1608–9 Dorset found reason to complain of his second wife's misconduct, and was negotiating with Archbishop Richard Bancroft and Lord Ellesmere for a separation from her when he died.