It has to be emphasized at the outset that, except for individual name changes, O Beirnes are not O Byrnes. The two lineages are unrelated and have different origins and histories. O Beirne is a western Ireland Family centered in eastern County Roscommon whereas O Byrne is an eastern Ireland Clan centered in Wicklow and earlier in Kildare. That they are quite separate was pointed out in the Annals of the Four Masters in the early 1600s and in other publications since. Nevertheless the names are still commonly confused merely because they sound alike.  

Present indications are that, in round figures, the original O Beirne ancestors came to Ireland a bit over 2000 years ago, or around 150 BCE (unless they were of Viking origin) and have been inhabitants of Roscommon for about 1800 years and a named unit for 1100, that their recorded history began nearly 900 years ago, and that they began significant emigration from Ireland 400 years ago and to North America in the last 200.

The O Beirnes originally were a Sept when they all lived in the same locality. They became a Family when they spread out. They were never a Clan or Sub Clan. In the Gaelic hierarchy up to the 1500s they were at the social level immediately below regional leaders such as the O Connors, Mac Dermotts, and O Kellys, which put them above a great many other families.
        They were listed as among the 104 most prominent of at least 3500 Families by Ida Grehan in Irish Family Names (1983) but not featured among the 199 leading Clans and Families of Ireland in Grenham's authoritative 1993 book on that subject, though mentioned.       None left a lasting mark on the history of Ireland. Family summaries mention as notable only a Steward to the King of Ireland in the 1100s, a Protestant Bishop in the early 1800s, and a British diplomat in the earls' 1900s. Robert J.  Scally's scholarly history of the 1800s in the Barony of' Ballintober North which contains the O Beirne ancestral territory,  The End of Hidden Ireland (1995) mentions only one O Beirne and that because he was hanged.  
        The first known human invasion of Ireland was eight or ten thousand years ago. Neolithic people came over a land connection between southwest Scotland and northeast Ireland that existed because the sea-level was lower than now. Later invaders had to come by sea. Animals that had not survived an ice age in Ireland also arrived over that land connection. Those such as snakes that travel only slowly did not get to it before it was submerged and thus never reached Ireland.  
        How many pre-Christian invasions there were is unclear: some supposed ones may really have been internal struggles for power. The first that is directly relevant to O Beirne history was by the fierce, short, black-haired Fir Bolgs or Belgae. They controlled Ireland until supposedly dispossessed except in Connacht by the mysterious Tuatha De Danann. Probably it was the later Celtic invaders who suppressed the Fir Bolg as each invasion was opposed by the people already there usually more or less unsuccessfully; and there was intermarrying between the races. In any event among the last strongholds of the Fir Bolg was the Slieve Bawn Hills just east of Strokestown and the Tulsk area to its west. They seemingly were subdued for some six centuries and then allegedly reappeared in the mid 800s as the O Mannachains (O Monaghans) in control of Tir Briuin Na Sinna in which was the O Beirne homeland.  
        The probability is that the O Beirnes originated with the last wave of Celtic invasion, that by the Menapii who were an important seafaring and trading tribe of Belgae that inhabited the North Sea coast of Gaul (hence Gaels) from the Rhine estuary south to what is now northern France. They were the only tribe of Celtic Gauls to remain free of Roman influence. One reason was that many emigrated to Britain and Ireland to evade it. In this respect those in Ireland were successful because the Roman plans of around 80 B.C. to conquer it were never implemented.