Henry was born the eldest son of Donogh O'Brien and Elizabeth FitzGerald.

His father's family were the O'Briens, an important Gaelic Irish dynasty, that descended from Brian Boru, medieval high king of Ireland.

[1] Henry's mother was the fourth daughter of Gerald FitzGerald, 11th Earl of Kildare and his wife Mabel Brown.

Henry and Mary had five daughters: O'Brien was summoned on 3 March 1613 as Lord Ibrickane to the Irish House of Lords of the Irish Parliament of 1613–1615, the only parliament of King James I in Ireland.

[13] He had no son and was succeeded in his titles by his brother Barnabas O'Brien, 6th Earl of Thomond.