At Oxford, Mayne met Edmund Campion and other Catholics, such as Gregory Martin, Humphrey Ely, Henry Shaw, Thomas Bramston, Henry Holland, Jonas Meredith, and Roland Russell.
At some point Mayne, too, became a Catholic.
Late in 1570, a letter addressed to him from Gregory Martin, urging him to come to Douai, fell into the hands of the Bishop of London, and he sent a pursuivant to arrest Mayne and others mentioned in the letter.
Warned by Thomas Ford, Mayne evaded arrest by going to Cornwall and then, in 1573, to the English College, Douai (now in northern France).

Mayne was ordained a priest in the Roman Catholic Church at Douai in 1575 and on 7 February in the following year he obtained the degree of Bachelor of Theology of Douai University.

On 24 April 1576, he left for the English mission in the company of another priest, John Payne.
He soon joined the household of Francis Tregian at Golden in the parish of Probus, Cornwall where he posed as his steward.
Francis Tregian (1548–1608) was one of the richest landowners in Cornwall.

Missionaries from Douai were looked upon as a papal agents intent on overthrowing the queen.
The authorities began a systematic search in June 1576, when the Bishop of Exeter William Bradbridge came to Cornwall.
On 8 June 1577, the High Sheriff of Cornwall, Richard Grenville, conducted a raid on Tregian's house during which the crown officers "bounced and beat at the door" to Mayne's chamber.
On gaining entry, Grenville discovered a Catholic devotional article, an Agnus Dei, around Mayne's neck, and took him into custody along with his books and papers.
At Oxford, Mayne met Edmund Campion and other Catholics, such as Gregory Martin, Humphrey Ely, Henry Shaw, Thomas Bramston, Henry Holland, Jonas Meredith, and Roland Russell. At some point Mayne, too, became a Catholic. Late in 1570, a letter addressed to him from Gregory Martin, urging him to come to Douai, fell into the hands of the Bishop of London, and he sent a pursuivant to arrest Mayne and others mentioned in the letter. Warned by Thomas Ford, Mayne evaded arrest by going to Cornwall and then, in 1573, to the English College, Douai (now in northern France).
Mayne was ordained a priest in the Roman Catholic Church at Douai in 1575 and on 7 February in the following year he obtained the degree of Bachelor of Theology of Douai University.
On 24 April 1576, he left for the English mission in the company of another priest, John Payne. He soon joined the household of Francis Tregian at Golden in the parish of Probus, Cornwall where he posed as his steward. Francis Tregian (1548–1608) was one of the richest landowners in Cornwall.
Missionaries from Douai were looked upon as a papal agents intent on overthrowing the queen. The authorities began a systematic search in June 1576, when the Bishop of Exeter William Bradbridge came to Cornwall. On 8 June 1577, the High Sheriff of Cornwall, Richard Grenville, conducted a raid on Tregian's house during which the crown officers "bounced and beat at the door" to Mayne's chamber. On gaining entry, Grenville discovered a Catholic devotional article, an Agnus Dei, around Mayne's neck, and took him into custody along with his books and papers.
Cuthbert Mayne