From the 5th century founding of Cenél nEógain, the tuatha was a sub-unit of the larger kingdom of Ailech (which they typically held the kingship to), along with their Cenél Conaill cousins, fellow descendants of Niall of the Nine Hostages. The initial ascent of Ailech had coincided with the decline of the Ulaid, whose kingdom of Ulster receded to the north-east coast.

Following the Norman invasion of Ulster in 1177, Tír Eoghain had become the predominant power in the north of Ireland, a position it regained upon the collapse of the Norman Earldom of Ulster in the 14th century. During the reign of Tudor monarch Elizabeth I it would become an earldom within the kingdom of Ireland, however the extent and power of Tyrone would be eventually curtailed and it was shired into the counties of Armagh and Tyrone, and subdivided into baronies.

During the reign of Stuart monarch James I, Tyrone would be reduced further with the barony of Loughinsholin in its north-east being transferred to the new county of Londonderry. The Ó Néill rebelled several times, attempts to reassert sovereignty. The last attempt of substance was under Hugh O'Neill, Earl of Tyrone, who fled in 1607 in what became known as the Flight of the Earls, where he and many of his allies (particularly among Ulster Gaeldom) fled Ireland.

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