Nuala made a dynastic marriage with Niall Garve O'Donnell, a cousin and a rival claimant to the O'Donnell lordship. After the marriage Niall Garve became an ally of her brother Hugh Roe and joined him after he took part in the 1594 Siege of Enniskillen, triggering the nine-year Tyrone's Rebellion. However Niall Garve, along with three of his brothers and many followers, dramatically switched sides and began assisting Crown forces under the English commander Sir Henry Docwra who were operating out of Derry. He led forces during the Crown victories at the Battle of Lifford (1600) and Siege of Donegal (1601), and had troops of the Royal Irish Army placed under his command. Niall's ambition was to have himself declared the Gaelic lord of Tyrconnell. When Nuala heard of her husband's defection, Nuala left him and returned to live with her brother Hugh Roe, taking some of her children with her. Nuala subsequently divorced Niall. When her brother Rory fled with Hugh O'Neill the Earl of Tyrone to Rome in 1607, Nuala, who had left her husband when he joined the English against her brother, accompanied him, taking with her her daughter, Grania.