His clan ultimately united with long-time enemies the O'Neills against the English – this alliance would continue into the Nine Years' War (1593–1603).

[2] Historian Francis Martin O'Donnell has named Sir Hugh's first wife as "Nuala, a daughter of O’Neill".

[10][11][12] According to historian Robert Dunlop, "for a long time past there had existed two parties in Tyrconnell" – those who supported an alliance with the English, and those who preferred to side with the O'Neills.

[1] According to historian Emmett O'Byrne, O'Donnell was "always too weak politically and militarily to deal with the combined challenges of the power of the O'Neills in Ulster, the extension of English control into north Connacht, and the strength of his rivals in Tyrconnell".

[20][21] These dynastic marriages would further cement a growing alliance between two Irish clans who had traditionally been mortal enemies for centuries.

[13] The Description of Ireland (1598) makes reference to this alliance: "This controversie was taken away by a double marriage, Tyrone having married [Hugh Roe]'s sister, by whom he hath diverse sons, and [Hugh Roe] having married his daughter..."[14] In late 1588, 23 ships of the Spanish Armada were lost on Ireland's coast.

[23][24] Upon hearing of the presence of Spanish fugitives there, Tyrone's mercenary forces, commanded by his foster-brothers Richard and Henry Hovenden, proceeded to Inishowen.

[25][26] Tyrone's instructions to the Hovendens are unknown;[27] ultimately his forces committed the largest single massacre of Armada survivors in Inishowen.

[22] Historians Marshall and Morgan characterise Tyrone as reluctantly ordering the massacre to keep in the English government's good graces.

[27][28] However, contemporary sources seem to imply that the massacre was carried out on the actions of the O'Donnell clan – O'Neill's forces were counselled by O’Donnell and Iníon Dubh.

[22][27] A 1614 history of Donegal Abbey references O'Donnell doing penance for his sins in his retirement, "the weightiest of which was a cruel raid on the wrecked Spaniards of the Armada, whom he slew in Innishowen, at the bidding of deputy Fitzwilliam".

O'Donnell offered thirty Spanish officers, taken from the Inishowen shipwreck, as prisoners in the hope to exchange them for his son, but this was unsuccessful.

[2] According to Philip O'Sullivan Beare, "[O'Donnell], after the manner of Irish Chiefs, devoted the seven years which he lived after this, to prayer and meditation on holy things".