They had a total of 14 children including his heir William (1631–1680), Thomas (1635-1683), Henry (1636–1659), George (1638–1672) and Elizabeth (1645–1724).

Several of his daughters died unmarried, as the financial losses he suffered during the civil war made it impossible to provide them with dowries.

The Brereton family had been established in Cheshire since the 14th century and was split into a number of different branches; the senior line was based at Handforth Hall and headed by another Sir William Brereton (1604–1661), a Puritan who led Parliamentarian forces in Cheshire during the civil war.

[5] He held no military commission during the First English Civil War but in August 1642 was appointed a Commissioner of Array for Cheshire by Charles I, and installed a Royalist garrison at Brereton Hall.

Captured in 1644 when Biddulph House in Staffordshire surrendered to Parliamentarian forces, he was restored to his estates by the Committee for Compounding with Delinquents after paying a fine of £2,539.