John Digby, 1st Earl of Bristol, was the fourth and youngest son of Sir George Digby (d. 1586), of Coleshill, Warwickshire, and of Abigail Heveningham of Ketteringham, Norfolk. He was educated at Magdalen College, Oxford, and later admitted to the Inner Temple in 1598. In November 1605 Lord Harrington, who had charge of Princess Elizabeth, sent Digby to inform King James I that the gunpowder plotters' plan to seize Elizabeth had failed. At Court Digby's charm, good looks and diplomatic ability quickly gained him the favour of the King, who made him a gentleman of the privy chamber. He was knighted on 16 March 1607, and on 31 May 1609 married Beatrice (1574?–1658), daughter of Charles Walcot of Walcot, Shropshire. Following his appointment as ambassdaor to Spain, he was created Baron Digby of Sherborne in 1618 and Earl of Bristol in 1622.

Digby was a leading figure in the unsuccessful Spanish Match, the effort to marry Prince Charles to the Infanta Maria Anna of Spain, daughter of Philip III, for which he was made a scapegoat and ordered to reside on his estates. After his refusal to accept responsibility in the failure of the match, Digby was impeached and sent to the Tower by Charles after his accession to the throne. Undaunted, Digby made counter-charges against George Villiers, 1st Duke of Buckingham, the prime royal favourite. Ominously for the King's reputation, the House of Lords decided to hear Digby in his own defence first. His trial never proceeded, although he remained in the Tower until 1628.

Following Buckingham’s assassination in August 1628, Digby eventually offered his services to the King and was formally reconciled with him. As the political crisis of the early 1640s mounted, Digby emerged as a trusted and moderate royal adviser, along with his son George, Lord Digby (1612-1677). 1641 saw a complete reconciliation between the two men: with Lord Bedford, Bristol became leader of the moderate Royalists in the House of Lords, working to achieve a compromise with John Pym, and save the Earl of Strafford's life. Bristol came increasingly to be seen as a ‘hardline’ royalist, which resulted in him being imprisoned by Parliament after the outbreak of the Civil War, although he was later allowed to join the King at Oxford. After the Battle of Edgehill he was one of the ‘moderate party’ who persuaded the King not to attempt to take London, which might have brought the war to a swift conclusion. After the King's defeat he moved to Paris and died there in 1653 aged 72.

Digby also sat to Johnson for the bust-length portrait dated 1628, now in the National Gallery of Ireland, Dublin (NGI.584), in which he is shown in a sculpted cartouche.