Norborne Berkeley was born about 1717 in Stoke Gifford, Gloucestershire, to John Symes Berkeley and Elizabeth Norborne. In 1726, at the age of nine, Berkeley was admitted to Westminster School but remained there for only a year. His political career began in 1741 when he was elected MP for Gloucestershire, a seat he held until 1763 when he left the House of Commons to pursue a peerage, the Barony de Botetourt, which had lain in abeyance since 1406. Considered a staunch Tory, Berkeley's fortunes were boosted considerably on the accession of George III in 1760 when he was appointed a Groom of the Bedchamber. He was named Lord Lieutenant of Gloucestershire in 1763 and then, in April 1764, his petition for the Barony was confirmed. Shortly thereafter he took a seat in the House of Lords as the 4th Baron de Botetourt and, in 1767, appointed Lord of the Bedchamber.

Having ruined his fortune in a failed mining project, by the late 1760s Botetourt was in serious need of a steady income. His allies in the British government, Lord Bute chief among them, found one for him as governor of Virginia, a position to which Botetourt was appointed on 29 July 1768. Although he proved to be very popular among many Virginians, he was to enjoy the post for only two years, dying in Williamsburg on 15 October 1770, after an illness lasting several weeks.

Botetourt never married and so left no direct heirs. It has been speculated that Sir Charles Thompson, a naval officer and baronet, born about 1740, was his illegitimate son. Botetourt was the legal guardian of his nephew, Henry Somerset, 5th duke of Beaufort, from the time of the death of the 4th duke in 1756. His niece was the celebrated Mary Isabella Manners, duchess of Rutland, a social and political rival of the duchess of Devonshire.