A leading opponent of Charles I of England, when the First English Civil War began in August 1642, he was appointed as the commander of Parliamentarian forces in Staffordshire and Warwickshire.

Many initially preferred him as commander of Parliamentarian forces to the Earl of Essex, while his conviction that "true religion" required belief in God, rather than a specific form of worship, prefigured later divisions between Presbyterians and Independents like Oliver Cromwell.

[1] His sister Dorothy (1605–1650) married Arthur Haselrig, who was one of the Five Members in January 1642, while Godfrey Bosvile (1596–1658), a half-brother from his mother's first marriage, became a close friend and political associate.

Many members were prominent in the Parliamentary opposition in 1640, including Pym, John Hampden, Francis Rous, Lord Saye and Sir William Waller.

[2] They dropped the idea when their proposed political constitution was rejected by John Winthrop of Massachusetts, who insisted only full church members be allowed to vote.

[11] Appointed Parliamentarian commander in Staffordshire and Warwickshire, on 23 August Greville repulsed an attempt by the Earl of Northampton to capture Warwick Castle.

[1] Greville's death was a serious blow, not least because his energy and commitment to defeating Charles militarily meant many viewed him as a better choice than the Earl of Essex, the current Parliamentarian commander.

According to Puritan diarist Lucy Hutchinson, Gell "had not understanding to judge the equity of the cause, nor piety, nor holiness", while his men were "the most licentious, ungovernable wretches that belonged to the Parliament".

[15] Despite a well-deserved reputation for religious radicalism, Brooke supported ministers with a wide range of views, including mainstream members of the Church of England.

[2] In a speech made in February 1643, Greville anticipated Cromwell in urging Parliament to resist hiring mercenaries or professionals in favour of those who "fought for the sake of the cause".