He was the son of Ralph Neville, 1st Earl of Westmorland, by his second wife, Joan Beaufort, a daughter of John of Gaunt. Despite being a younger son, he was able to make a great marriage, to Alice Montagu, Countess of Salisbury, probably due to his royal descent on his mother's side.
After his marriage (1420) Salisbury was given high posts in the north of England, including Warden of the Western March 1420 - 1435. He was also Constable at the coronation of his cousin Henry VI.
However Salisbury turned to the cause of the Duke of York, fighting on that side at the first Battle of St Albans and at Blore Heath. He was beheaded the day after the Battle of Wakefield.
Amongst Salisbury's children were Richard Neville, Earl of Warwick and John Neville, 1st Marquess of Montagu.