One of five surviving children, William had two brothers, John (1624–1656) and Edward, along with two sisters; Jane (died 1648), and Mary (died 1652), whose second husband was another member of the Gerard family, Sir Gilbert Gerard, 1st Baronet of Fiskerton (died 1687).[2]
In 1629, Brereton married Lady Elizabeth Goring (1615–1687), daughter of George Goring, 1st Earl of Norwich and another substantial Cheshire family. 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.[3]
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.[4] In 1624, Brereton's grandfather purchased an Irish barony and was appointed Baron Brereton of Leighlin in Leinster, a title inherited by his grandson along with his lands when he died on 1 October 1631.[5]