Berkeley was the third son of John Berkeley, 1st Baron Berkeley of Stratton, by Christiana, daughter of Sir Andrew Riccard. Charles, a naval captain who held the title for two years, and John, an admiral who held the title for 16 years, were his elder brothers. William lived a much longer life. He was born on an unknown date between John's 1663 birth and 23 March 1672 which would have made William a septuagenarian by the time of his death in 1741.
Lord Berkeley of Stratton married Frances, daughter of Sir John Temple and Jane Yarner; her sister Jane having married his elder brother. Lord Berkeley and his wife had several children, including the Honourable Frances, who married William Byron, 4th Baron Byron, and was the mother of William Byron, 5th Baron Byron, and of Admiral John Byron. Lady Berkeley of Stratton died in July 1707. Lord Berkeley of Stratton remained a widower until his death at Bruton, Somerset, in March 1741. He was succeeded by his eldest son, John.