Even as a young woman O'Malley was involved in the business of sailing ships and international trade. It is known that she wanted to join the fleets of her father's large shipping and trading business, but he always refused. When her father died, O'Malley inherited his business. From her mother she inherited land, and from her first husband, Dónal an Chogaidh (Dónal "the warlike") O'Flaherty, she inherited property and holdings, all of which allowed her to become very wealthy, reportedly owning as much as 1000 head of cattle and horses.
Around the time of her first husband's death came the initial complaints to the English Council in Dublin from Galway's city leaders that O'Flaherty and O'Malley ships were behaving like pirates. Because Galway imposed taxes on the ships that traded their goods there, the O'Flahertys, led by O'Malley, decided to extract a similar tax from ships travelling in waters off their lands. O'Malley's ships would stop and board the traders and demand either cash or a portion of the cargo in exchange for safe passage the rest of the way to Galway. Resistance was met with violence and even murder. Once they obtained their toll, the O'Flaherty ships would disappear into one of the many bays in the area.
By the early 1560s, O'Malley had left O'Flaherty territory and returned to her father's holdings on Clare Island. She recruited fighting men from both Ireland and Scotland, transporting the gallowglass mercenaries between their Scottish homes and Irish employers and plundering Scotland's outlying islands on her return trips. In an apparent effort to curry favour with the English, O'Malley went to the Lord Deputy of Ireland and offered two hundred fighting men to serve English interests in Ireland and Scotland.
When her her lover, Hugh de Lacy, the shipwrecked son of a Wexford merchant she had rescued, was murdered by the MacMahon clan, O'Malley waited for the culprits to land on the holy island of Caher for a pilgrimage. O'Malley then captured their boats, and the MacMahons themselves and killed those responsible for her lover's death. Still not satisfied with her revenge, O'Malley then sailed for Ballycroy and attacked the garrison at Doona Castle, overpowering the defenders and taking the castle for herself. Her attack against the MacMahons was not the first time she interrupted someone at their prayers. Legend tells of another chieftain who stole property from O'Malley and fled to a church for sanctuary. She was determined to wait out the thief, maintaining that he could starve or surrender. The thief dug a tunnel and escaped, however, and the hermit who took care of the church broke his vow of silence to scold her for attempting to harm someone who had sought sanctuary. Her reply is not recorded.
When her brother and two of her sons were taken captive by the English governor of Connacht, Sir Richard Bingham, O'Malley sailed to England to petition for their release. She formally presented her request to Elizabeth I at her court in Greenwich Palace. O'Malley refused to bow before Elizabeth because she did not recognise her as the Queen of Ireland. It is also rumoured that O'Malley had a dagger concealed about her person, which guards found upon searching her. Elizabeth's courtiers were said to be very upset and worried, but O'Malley informed the queen that she carried it for her own safety. Elizabeth accepted this and seemed untroubled. Some also reported that O'Malley sneezed and was given a lace-edged handkerchief from a noblewoman. She apparently blew her nose into the handkerchief and then threw the piece of cloth into a nearby fireplace, much to the shock of the court. O'Malley informed Elizabeth and her court that, in Ireland, a used handkerchief was considered dirty and was destroyed. Their discussion was carried out in Latin, as O'Malley spoke no English and Elizabeth spoke no Irish. After much talk, the two women came to an agreement. Included in the stipulations for each party, Elizabeth was to remove Sir Bingham from his position in Ireland and O'Malley was to stop supporting the Irish lords' rebellions.
The meeting seemed to have done some good for Richard Bingham was removed from service. But several of O'Malley's other demands (including the return of the cattle and land that Bingham had stolen from her) remained unmet, and within a rather short period of time Elizabeth sent Bingham back to Ireland. Upon Bingham's return, O'Malley realised that the meeting with Elizabeth had been useless, and went back to supporting Irish insurgents during the Nine Years' War. She most likely died at Rockfleet Castle around 1603, the same year as Elizabeth, though the year and place of her death are disputed.
