The O'Byrnes derive their ancestry from King Milesius, who came from Spain to Ireland in 558 B.C., and his son Heremon. The O'Byrne name itself is derived from bran, Irish for raven. It has long been a leading sept in east Leinster and is now one of the most numerous names in Ireland. Byrne is a derivative.

In Co. Wicklow, homeland of the O'Byrnes, the remains of Black Castle can be seen on the cliff edge at Wicklow town. This castle was a successor to that built in 1169 by Maurice Fitzgerald, an Anglo-Norman, to try and keep the O'Byrne chieftains at bay, because they were constantly raiding the town. One of the clan, Fiach MacHugh O'Byrne (1544-1597), then the clan chieftain, defeated an English army under Lord Gray at Glenmalure, near the great mountain of Lugnaquilla. The site of the battle can still be seen.

Two Byrnes are prominent in show business, Gay Byrne, the Irish broadcaster, and Gabriel Byrne, the Hollywood film actor, both of whom were born and brought up in Dublin.