He was noted as one of the most promising pupils of Pietro Martire Vermigli, and on Mary's accession obtained leave from his college to travel abroad.

He lived at Basel, Zürich, Frankfurt and Geneva, making the acquaintance of the leading Swiss divines, whose ecclesiastical views he adopted.

Humphrey returned to England at Elizabeth I's accession, was appointed Regius Professor of Divinity at Oxford in 1560, and was recommended by Archbishop Parker and others for election as President of Magdalen College.

The fellows refused at first to elect so pronounced a reformer, but they yielded in 1561, and Humphrey gradually converted the college into a stronghold of Puritanism.

Parker, in fact, was not supported by the council; in 1566 Humphrey was selected to preach at St Paul's Cross, and was allowed to do so without the vestments.

In 1578 he was one of the divines selected to attend a diet at Schmalkalde to discuss the project of a theological accommodation between the Lutheran and Reformed churches; and in 1580 he was made Dean of Winchester.