Born in England in 1705, he was the eldest surviving child of Lucius O'Brien (1675-1717 d.v.p) and Catherine Keightley (1676- c. 1733).
He inherited the baronetcy from his grandfather Sir Donough O'Brien, 1st Baronet as his own father had pre-deceased him.
His maternal grandmother, Lady Frances Keightley (née Hyde) was the sister of Anne Hyde Duchess of York who in turn was the mother of Queen Mary II and Queen Anne.
He entered the Irish House of Commons in 1727, sitting for County Clare, the same constituency his grandfather had also represented, until his death in 1765.
[2] Edward lived extravagantly and gambled heavily on horse races, destroying the wealth which his grandfather had so carefully built.