Tirlough Brassileagh O'Neill was the son of Phelim Caoch O'Neill, Prince of the Cenél nEógain.
As the grandson of Conn O'Neill, then King and later Earl of Tyrone, he was fostered by the McCann clan in the area to the south of Lough Neagh known as clan Brassill area.
When Tirlough's father died in 1542, he and his family were quickly pushed aside by the internal politics of O'Neill dominated Ulster. As a son of Conn Bacach, he would eventually be able to attempt a try at the Chiefship of all the O'Neills, and thus was seen as a threat by his uncles Shane O'Neill (nicknamed "An Diomas" or "the Proud") and Mathew Kelly (Ferdocha), Baron of Dungannon.
In spite of his uncles warfare and attempts to push Tirlough out, he eventually outlived both uncles and grew to some importance in the turmoil of the later 16th century. Turlough stood for election as The O'Neill Mor in 1583 when it was thought that Sir Tirlough O'Neill, the reigning O'Neill Mor had died, and led sizable groups of fighting men in 1575 and throughout the 1590s during the Nine Years War. He is listed as having the ability to raise "50 Horse and 200 foot" soldiers out of his territories at 24 hours notice to fight.
He again made a bid for the Chiefship in the 1590s, but his cousin, Hugh O'Neill, 3rd Earl of Tyrone, bought him off with a gift of territory. In 1595 the English make reference to him as being part of the leadership in Ulster, but too old to worry about, and he died sometime after.
Turlough Brassileagh was married to an Anabla O'Reilly, a daughter of The O'Reilly of Cavan. They had children: Con McTirlough, and Hugh McTurlough. These sons were fought in the 9 Years War, raided neighboring clans, and fought in the 1608 Rebellion.