Cottington was ambassador to Spain in 1616–17 under King James I. In 1629 James's successor, Charles I, made him chancellor of the exchequer and again sent him to Spain as ambassador. In 1631 Cottington signed a secret treaty with Spain. As a reward he was made a baron. His prominence in Charles's council and his Roman Catholic and Spanish sympathies earned him the enmity of Puritans in Parliament. He opposed their attack on Thomas Wentworth, Earl of Strafford, unsuccessfully urging the king not to yield to demands for the earl's execution. Cottington was ousted from his chancellorship in January 1642.

After Charles went to war with the Parliamentarians, Cottington was made lord treasurer (October 1643). He fled to the European continent upon the surrender of Charles's forces in 1646. In 1649 Cottington attempted, without success, to obtain Spanish aid for the Royalist cause. He then settled in Valladolid, where he died. All his children predeceased him, and the barony became extinct.