Born Edward Hugessen Knatchbull, he was the younger son of Sir Edward Knatchbull, 9th Baronet, of Mersham Hatch, who twice served as Paymaster-General, and his second wife Fanny Catherine Knight, who was a niece of author Jane Austen. In 1849 he assumed by Royal license the additional surname of Hugessen, which was the maiden surname of his father's mother. Knatchbull-Hugessen was educated at Eton and Magdalen College, Oxford, where he was President of the Oxford Union.
In 1857 he was elected Member of Parliament for Sandwich, a seat he would hold until 1880. He served as a Government Whip under Lord Palmerston from 1859 to 1860; as Under-Secretary of State for Home Affairs under Lord Russell in 1866 and under Gladstone from 1868 to 1871; and as Under-Secretary of State for the Colonies under Gladstone from 1871 to 1874.
Knatchbull-Hugessen was admitted to the Privy Council in 1873 and in 1880 he was raised to the peerage as Baron Brabourne, of Brabourne in the County of Kent.
He edited the first edition of Jane Austen's letters, published in 1884. This edition included about two-thirds of her surviving letters, and was dedicated to Queen Victoria. He inherited the letters after his mother's death in December 1882.
Lord Brabourne died in February 1893, aged 63.