He was educated at Christ Church, Oxford, afterwards travelling on the Continent for some years between 1578 and 1583. In 1585 he was elected member of parliament for Glamorganshire; and in the same year he went with his elder brother, Sir Philip Sidney to the Netherlands, where he served in the war against Spain under his uncle Robert Dudley, Earl of Leicester. He was present at the Battle of Zutphen where Sir Philip Sidney was mortally wounded, and remained with his brother.
After visiting Scotland on a diplomatic mission in 1588, and France on a similar errand in 1593, he returned to the Netherlands in 1506, where he rendered distinguished service in the war for the next two years. He had been appointed governor of Flushing in 1588, and he spent much time there till 1603, when, on the accession of James I, he returned to England. James raised him at once to the peerage as Baron Sidney of Penshurst, and he was appointed chamberlain to the queen consort, Anne of Denmark. In 1605 he was created Viscount Lisle, and in 1618 Earl of Leicester, the latter title having become extinct in 1588 on the death of his uncle, whose property he had inherited.
Leicester was a man of taste and a patron of literature, whose cultured mode of life at his country seat, Penshurst, was celebrated in verse by Ben Jonson. It was at Penshurst that he died. He had been married twice; first to Barbara, a noted heiress and beauty, the daughter of John Gamage, a Glamorgan gentleman; and secondly to Sarah, daughter of William Blount, and widow of Sir Thomas Smythe. By his first wife he had a large family. His eldest son having died unmarried in 1613, Robert, the second son, succeeded to the earldom; one of his daughters married Sir John Hobart, ancestor of the Earls of Buckinghamshire.