Wadham, Nicholas, benefactor of Wadham College, Oxford, was probably born at the family seat, Merrifield, near Ilton, Somerset, the only son of John Wadham (d. 1578) and his wife, Joan (d. 1583), daughter of John Tregarthin and widow of John Kellaway.

The Wadhams had been at Edge Manor, Branscombe, in south Devon since the late fourteenth century. Sir John Wadham (d. 1412), justice of the common pleas, acquired extensive properties in Devon and Somerset, augmented through the fifteenth century by a series of marriages to heiresses. Nicholas Wadham's grandfather Sir Nicholas (d. 1542) was at various times sheriff of Somerset and Dorset, of Devon, and of Wiltshire. Sir Nicholas's youngest son, also Nicholas (d. 1551), was a member of Thomas Cromwell's household, subsequently holding court office as a gentleman pensioner, and commanding troops in Boulogne from 1544. John Wadham was less prominent than his father, but was sheriff of Somerset and Dorset in 1556–7 and retained a place on the Somerset commission of the peace until his death in 1578.