William' father, Robert, had been an improving landlord who died of a fever contracted while visiting his tenants during the Great Famine in 1847.
He was responsible for the "Gregory Clause" which said that anyone applying for relief during the Great Famine would not be eligible if they were occupying more than 1⁄4 of an acre (0.1 ha).
After the death of his father and following his failure to retain his seat in the general election of 1847 he took up residence on the family estate at Coole Park in County Galway.
In 1859 he travelled through North America, befriending several southern Congressmen, including James Murray Mason of Virginia and William Porcher Miles of South Carolina.
He also argued that Britain should pursue a strong anti-Turkish policy, and supported the cession of the Ionian Islands and Crete to Greece.
In domestic affairs Gregory was active in defending the Roman Catholic clergy in Ireland and working for land reform.
On 10 July 1871 Gregory was made a member of the Privy Council of Ireland and in the following year he was appointed Governor of Ceylon (now Sri Lanka).
He bequeathed the important painting Christ in the House of Martha and Mary by Diego Velázquez, along with three other works including a Jan Steen, to the National Gallery, London of which he had been a Trustee from 1867 onwards.
At the time of Lady Gregory's death in 1932, the land had already been sold to former tenants so she was buried with her sister at Bohermore Cemetery near Galway.