He is mainly remembered now for having facilitated the much-discussed marriage of Hugh O'Neill, Earl of Tyrone and his third wife Mabel Bagenal, which took place at Warren's home, Drumcondra Castle, in 1591.
He enjoyed the confidence of three successive monarchs, and was a close associate of Thomas Radclyffe, 3rd Earl of Sussex, Lord Deputy of Ireland 1556-1558.
Another powerful connection was Sir Conyers Clifford, Lord President of Connaught (died 1599), who was William's second cousin on his mother's side.
William and his brother Henry continued this family tradition of advantageous marriages: Henry married Alice Loftus, daughter of Adam Loftus, Archbishop of Dublin and his wife Jane Purdon, and William, sometime after 1586, married Jenet Finglas, daughter of Patrick Finglas of Westphailstown and widow of John Bathe, Chancellor of the Irish Exchequer.
At a time when Irish office holders were required to take the Oath of Supremacy, recognising Elizabeth I as head of the Church of Ireland, Warren was suspected, probably with good reason, of privately sharing his wife's religious beliefs.
[3] He was given a military command, and in April 1586 he was entrusted by the Lord Deputy of Ireland, Sir John Perrot, with the task of negotiating with Sorley Boy MacDonnell, a powerful Scottish chieftain who had challenged the authority of the English Crown by establishing a political base in County Antrim.
Whether it was a genuine love marriage (as suggested in the play Making History by Brian Friel) or whether it was an effort by O'Neill to form a political alliance with Mabel's powerful family is debatable.
By 1596 Warren's loyalty was so dubious that, despite being seriously ill, he was summoned to a hearing before the Irish Privy Council, where he was reprimanded and threatened with imprisonment, although the threat was not carried out.