He supported the Parliamentarian cause in the Wars of the Three Kingdoms, when he was known as Viscount Lisle, a subsidiary title of the Earls of Leicester.

His younger brother Algernon Sydney fought for Parliament in the First English Civil War, denounced Oliver Cromwell as a tyrant, and was executed for treason in 1683 for alleged involvement in the Rye House Plot.

He survived Pride's Purge in 1648 to sit in the Rump Parliament and was a councillor of state from 1648 to 1650.

On the restoration of King Charles II in 1660 Lord Lisle received a pardon.

An illegitimate daughter, Philadelphia Saunders, married Colonel John Shrimpton, later MP for Whitchurch, Hampshire and Governor of Gibraltar.