In 1581 he had a controversy with the Jesuit Edmund Campion, and published at Oxford his arguments in 1638 under the title, Piissimi et eminentissimi viri Tobiae Matthew, archiepiscopi olim Eboracencis concio apologetica adversus Campianam.
On his release he went to London, where he was a member of the association of young men founded in 1580 to assist the Jesuits Edmund Campion and Robert Parsons.
In 1580 he was selected, along with Edmund Campion, a former associate at Oxford, and others, to undertake a secret religious and political mission to England.
In 1581 Campion was arrested, but Parsons made his escape to Rouen, whence he returned to Rome, where he continued to direct the English mission.
During his term of office there took place the troubles in Rome concerning the English college and the subsequent Jesuit rule over that institution; and in 1580 the first Jesuit mission, headed by the redoubtable Robert Parsons and the saintly Edmund Campion, set out for England.