He was born at Docking, Norfolk, in 1558, the eldest son of Christopher Walpole, by Margery, heiress of Richard Beckham of Narford, and was educated at Norwich School, Peterhouse, Cambridge, and Gray's Inn. He was present at the execution of Edward Campion, and his clothes were sprinkled with Campion's blood. Walpole then converted to Roman Catholicism, gave up his law practice and followed in Campion's footsteps. He went by way of Rouen and Paris, toReims, where he arrived, 7 July 1582. On 28 April 1583, he was admitted into the English College, Rome, and in October received minor orders. On 2 February 1584, he became a probationer of the Society, and soon after went to France, where he continued his studies, chiefly at Pont-à-Mousson. He was ordained subdeacon and deacon at Metz, and priest at Paris, 17 December 1588.
After being twice imprisoned at Newgate for religion in 1586, Walpole arrived at Reims, 23 December 1589; he was ordained subdeacon at Laon, 23 September 1589, deacon and priest at Soissons, 17 March and 18 March 1590, was sent on the mission the following 9 April, and landed at Whitby. After acting as chaplain to the Spanish forces in theNetherlands, suffering imprisonment by the English at Flushing in 1589, and being moved about to Brussels, Tournai,Bruges, and Spain, he was at last sent on the mission in 1590. He was arrested shortly after landing at Flamborough for the crime of Catholic priesthood, and imprisoned at York. The following February he was sent to the Tower, where he was frequently and severely racked. He remained there until, in the spring of 1595, he was sent back to York for trial, where he was hanged, drawn and quartered on 7 April 1595. With him suffered Alexander Rawlins, of the Diocese of Gloucester. He was canonized as one of the Forty Martyrs of England and Wales.
