They belong to the Dál gCais kindred and are distant cousins to the O'Brien dynasty, but have since the Middle Ages been based not in County Clare, from where they originated, but in County Limerick.

According to historian C. Thomas Cairney, the O'Gradys were one of the chiefly families of the Dal gCais or Dalcassians who were a tribe of the Erainn who were the second wave of Celts to settle in Ireland between about 500 and 100 BC.

Some of the O'Grady family converted to the Church of Ireland (Anglican Communion) and produced a Bishop of Meath, Hugh Brady.

The family also produced some prominent historians such as Standish Hayes O'Grady and Standish James O'Grady, as well as Henry Fox Talbot, inventor, scientist and photography pioneer, and the Australian poet David Musgrave.

The now extinct title in the peerage of Ireland, the Viscount Guillamore, was held by the family.