The surname comes from the Irish Ó hEidirsceoil, grandson of Eidirsceol (from eidirsceol, meaning "go-between" or "bearer of news"). The original Eidirsceol from whom descent is claimed is reputed to have lived in the mid tenth century. Personal names associated with the family in its early years were Finn and Con or Mac Con, later anglicized as Florence and Cornelius The name is one of the very few to be clearly identified with the Érainn, or Fir Bolg, Celts who were settled in Ireland well before the arrival of the Gaels. Although the evidence is sparse, before the eighth century A.D. what is now Co. Cork appears to have been populated mainly by tribes of Érainn descent, including the Corca Laoighde tribal grouping of whom the Uí hEidirsceoil were the chief family. The encroachment southwards of the Gaelic Eoghanacht of Cashel from the eighth century on resulted in the assimilation or displacement of all of the original Érainn tribes. In the case of the Corca Laoighde, this displacement was towards the south-west of the county, into an area which later became part of the diocese of Ross, roughly defined by the modern towns of Roscarbery, Skibbereen, Schull and Baltimore. Baltimore was the seat of O’Driscolls, and gets its name ("Baile an Tighe Mór") from their castle or great house. From the twelfth century, the Annals describe the O’Driscolls as kings of the Corca Laoighde. A further indication of their power comes in their inclusion in the Gaelic genealogies; although they were not ethnic Gaels, a lineage was produced for the family to connect them to Lughaidh Laidhe, a supposed descendant of Milesius, the progenitor of the Gaels. Such was respectability in medieval Ireland. Given the nature of the land they occupied, with its wild twisting coastline, and their constant fight against the encroaching pressures of the Eoghanancht, the Anglo-Normans and the English, it is not surprising that the O’Driscolls became expert seafarers with a reputation for ferocity. From the thirteenth to the fifteenth centuries they struck an alliance with the Powers of Co. Waterford in their long feud with the burgesses and merchants of Waterford city, and many of their leaders were killed in battle on land and sea. One of the best known incidents occurred in 1413, when the Mayor of Waterford, Simon Wicken, arrived in Baltimore on Christmas Day and was invited to join in the Christmas festivities. He did, and enjoyed the company so much that he took O’Driscoll and his family back to Waterford, as prisoners. From the fifteenth century on, the family struggled to retain their lands and power against the English. Some indication of the strength of awareness of the past can be found in the history of the surname itself: in 1890, over 90% of those bearing the name recorded themselves as "Driscoll" while today, in a remarkable reversal of the nineteenth-century trend, virtually all are called "O'Driscoll". Their arms reflect the family's traditional prowess as seafarers, developed during their long lordship of the sea-coast around Baltimore.

And another account,

O'Driscoll (and its derivative Driscoll) is an Irish surname stemming from the Gaelic Ó hEidirsceoil clan. The O'Driscolls were rulers of the Dáirine sept of the Corcu Loígde until the early modern period. Their ancestors were Kings of Munster until the rise of the Eóganachta in the 7th century. At the start of the 13th century, three prominent branches of the family came into existence: O'Driscoll Mor, O'Driscoll Og, and O'Driscoll Beara. The Ó prefix was dropped by many in Ireland during the 17th and 18th centuries. The surname is now most prominent in the Irish counties of Cork and Kerry.

The surname derives from the forename Eidirsceol, who was alive in the early-to-mid 10th century. The Irish word itself, eidirsceol, means "go-between" or "bearer of news".

The family are of Érainn, descent, specifically the Corcu Loígde population group. By the time the family began using the surname, the territory known as Corcu Loígde (roughly the same as the diocese of Ross) in south-west County Cork, was identified as their homeland, with the town of Baltimore been their seat. From the 12th century the Ó hEidirsceoil's were recorded as kings of Corcu Loígde.

Been driven so far south by the Gaelic Eóganachta and the Anglo-Normans, the family became expert sailors and fishermen. According to John Grenham:

From the thirteenth to the fifteenth centuries they struck an alliance with the Powers of County Waterford in their long feud with the burgesses and merchants of Waterford city, and many of their leaders were killed in battle on land and sea. The feud ended when one of the best known incidents occurred in 1413, when the Mayor of Waterford, Simon Wicken, arrived in Baltimore on Christmas Day and was invited to join in the Christmas festivities. From the fifteenth century on, the family struggled to retain lands and power taken by the English. By 1610, Baltimore had become an English port. In 1631 the town was sacked by Algerine pirates who according to the Irish poem, "Only Smiled; O'Driscolls Child", the pirates burned, raided and kidnapped their people. The poem describes a brave O'Driscoll girl who fought back against the pirates. The poem further describes that, "High on a gallows tree a yelling wretch is seen: Hackett of Dungarvan steered the Algerine". "Some mutter'd of MacMurchadh who brought the Norman O'er. Some curs'd him with Iscariot, that day in Baltimore!"

They are described by Donnchadh Ó Corráin as follows:

In general, the seafaring peoples of the south and west coast—Ua hEtersceóil, Ua Muirchertaig, Ua Conchobair Chiarraige, Ua Domnaill of Corcu Baiscind, Ua Flaithbeartaig, Ua Dubda, and others served as commanders of the king's fleets.

Though the landowners of the clan lost several castles during the 17th century war with Queen Elizabeth of England, most of those bearing the name in Ireland are still to be found living in the County Cork.

Forenames associated with the family included Finn and Con/Mac Con. From the late medieval era, they were anglicized as Florence and Cornelius.