He was the son of Edmund Stafford, 5th Earl of Stafford, and Anne of Gloucester, daughter of Thomas of Woodstock and a grand-daughter of Edward III of England.
When Henry was a small child his father died and he became 6th Earl of Stafford, inheriting a large estate with lands in more than a dozen counties.
In 1444 he was created 1st Duke of Buckingham for his military services in France. He died at the Battle of Northampton.
Humphrey had two sons, who married first cousins with the same name. The eldest, Humphrey, Earl of Stafford (d. 1455), married Margaret Beaufort, daughter of Edmund Beaufort, 2nd Duke of Somerset. The younger, Lord Henry Stafford (d. 1481), married Margaret Beaufort, daughter of John Beaufort, 1st Duke of Somerset and widow of Edmund Tudor.
His eldest son having already died, Humphrey was succeeded by his grandson Henry.
{| border="2" align="center"
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|width="30%" align="center"|Preceded by:
New Creation
|width="40%" align="center"|Duke of Buckingham
|width="30%" align="center" rowspan="2"|Followed by:
Henry Stafford
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|width="30%" align="center"|Preceded by:
Edmund Stafford
|width="40%" align="center"|Earl of Stafford
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