That same year Desmond, having sided, as had his father, with the House of York, put down a Lancastrian invasion of Ireland by John and Thomas Butler, brothers of the Earl of Ormond.

The parliament in the Dublin Pale had a negative view of the Gaels, descendants of the original inhabitants, and passed an act in 1465 that every Irishman dwelling in the Pale was to dress and shave like the English, and take an English surname such as the name of a town, or of a colour such as Black, Brown, Green or White, or of a trade such as Smith, Carpenter, Thatcher, or forfeit his goods.

Another measure forbade ships from fishing in the seas off Ireland because the dues went to make the Irish people prosperous.

Following his assassination, in 1468 Edward IV replaced Desmond as Lord Deputy with John Tiptoft, 1st Earl of Worcester, a Crown servant notorious for his cruelty and ruthlessness, who was nicknamed "the Butcher of England".

Accused by his political enemies of treason, for aiding the Irish against the King's subjects, as well as extortion, Desmond attended a Parliament held in Drogheda.

Later accounts suggested that Edward IV's Queen, Elizabeth Woodville, was the prime mover, having taken offence at some tactless remarks of Desmond, which drew attention to her obscure birth, a subject on which she was understandably sensitive, as her husband had been ridiculed for marrying one who was "not the daughter of a Duke or earl".

[7] The Queen was undoubtedly a formidable enemy: her husband's biographer describes her as a woman who was cold and calculating by nature, "quick to take offence and reluctant to forgive"[8] but there is no contemporary evidence of any quarrel between her and Desmond.