He accompanied Edmund Campion (who was later canonized) on Campion's mission to aid English Catholics in 1580.
The Jesuit General, Everard Mercurian, had been reluctant to involve the Jesuits directly in the political machinations of the pope against England. The mission was further compromised because the pope had sent a separate group, unbeknownst to the Jesuit mission, to support the Irish rebel, James Fitzmaurice Fitzgerald. Parsons and Campion learned of this in Reims while en route to England. After Campion's capture, torture, and execution, Parsons left England, never to return.
Recalled to Rome in 1585, he was professed there 7 May, 1587 and sent to Spain at the close of 1588, to conciliate King Philip, who was offended with Father Acquaviva. Persons was successful, and then made use of the royal favour to found the seminaries of Valladolid, Seville, and Madrid (1589, 1592, 1598) and the residences of San-Lucar and of Lisbu (which became a college in 1622). Already in 1582 he had founded a school at Eu, in Picardy, in France, the first English Catholic boys' school since the Reformation; and he now succeeded in establishing at St Omer (1594) a larger institution to which the boys from Eu were transferred, and which, after a long and romantic history, still flourishes as Stonyhurst College at Stonyhurst.
In 1596, in Seville, he wrote Memorial for the Reformation of England, which gave in some detail a blueprint for the kind of society England was to become after its return to the faith.
He had hoped to succeed Allen as Cardinal on the latter's death. Unsuccessful, he was rewarded with the rectorship of the English College at Rome, the most important seminary for English Catholic priests.