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Incorporating Hanna's smaller work, Ohio Valley Genealogies, along with lists of first landowners, early marriages (to 1841), will records (to 1861), and burial records, this book is the premier reference work on the Ohio Valley. Concerned chiefly with a record of names and events, it bears reference to upwards of 50,000 pioneers, most of them Pennsylvanians and Revolutionary War bounty holders who ventured into this region of eastern Ohio. So far as it goes, the book is a factual recitation of the names of all those found in the records and annals of the late 18th and early 19th centuries.

The first part of the book consists of a general history of the first settlers (Scotch-Irish, Quakers, Germans) and the early churches. The second and third parts, however, contain genealogical matter of wide scope and importance, with extensive alphabetical lists of the county's land, marriage, burial, and will records, and detailed genealogies of the first settlers, showing date and place of birth and death, place of residence, name of wife and date of marriage, names of children and grandchildren, and dates and places of birth.