Samuel Neilson was born on 17 September 1761 at Ballyroney, Co. Down, to Alexander Neilson, a Presbyterian minister, and his wife Agnes. He was the second-born of a large family of eight boys and five girls and was educated in liberal arts and mathematics. He married Anne Bryson in 1785 when he worked as a successful woollen draper in Belfast and they had five children. Prior to his involvement with politics, Neilson’s business, the Irish Woollen Warehouse, was ‘the most extensive and respectable house in that line in Belfast’, generating the small fortune of £8,000 by 1792.
