He attracted the attention of Sir Henry Savile, who aided him in his studies, and about 1582 made the acquaintance of John Hotman, a learned French Protestant in the service of the Earl of Leicester.
In 1582 and 1583 he corresponded regularly with Hotman, and some of these letters, which prove strong affection between the writers, are printed in 'Francisci et Joannis Hotomanxorum...Epistolae' (Amsterdam, 1700).
In the following August he visited London to deliver to the queen those important dispatches in which Essex excused himself for his delay in suppressing Tyrone's Rebellion.
He was deeply interested in Essex's reinstatement at court, both on grounds of personal ambition and of affection for his employer, and, now that few friends had access to the earl, was much in his confidence.
He urged him to seek at all hazards an interview with the queen, and argued that Elizabeth would be unable to withhold her favour from him after she had heard from his mouth the story of his grievances and of the animosity with which the Cecils, Raleigh, and others regarded him.
Cuffe had no clear ideas as to the details of his policy, and did not take part in the secret meetings of Essex's friends, whom he had helped to bring together, at Drury House, in November and December 1600.
But Cuffe appealed to the good nature of his master's friend, the Earl of Southampton, who readily obtained from Essex a rescission of the order (see Wotton).
When Essex, just before his execution, requested to be confronted with Cuffe in the Tower (21 Feb 1600/1) in the presence of witnesses, he used the words: 'You have been one of the chiefest instigators of me to all these my disloyal courses into which I have fallen.'
At the end of February Cuffe answered several questions respecting Essex's negotiations with King James of Scotland which the lords of the council put to him.
Coke, the attorney-general and prosecuting counsel, denounced Cuffe in the strongest terms, and began his address to the court with the remark that he 'was the arrantest traitor that ever came to that bar,' 'the very seducer of the earl,' and 'the cunning coiner of all plots.'
Bacon in the official 'Declaration of the Treasons,' 1601, describes Cuffe as 'a base fellow by birth, but a great scholar, and indeed a noble traitor by the book, being otherwise of a turbulent and mutinous spirit against all superiors.'
58, are to be found Aphorismes Political, gathered out of the Life and End of that most noble Robert Devereux, Earle of Essex, not long before his death, a work which is also ascribed to Cuffe.
Cuffe assisted Columbanus in his edition (p. 2, Florence, 1598) of Longus's Pastoral of Daphnis and Chloe, and contributed six Greek elegiacs to William Camden's Britannia.