In The Pioneers, McCullough, perhaps best known for his books John Adams and 1776, traces the lives of several of the early settlers of America's Northwest Territory from just after the American Revolution to roughly the Civil War. In case you're not familiar with the term, the "Northwest Territory" is in reference to the giant piece of land that today mostly makes up Ohio, Indiana, Illinois, Michigan, and Wisconsin.
The book primarily revolves around the story of a handful of characters--most of whom are white New Englanders--who settled in and around Marietta, Ohio on the Ohio River. Chief among these are a minister named Manasseh Cutler and his son Ephraim. The book does a notable job of helping readers really understand what life, with all its many dangers, was like for those early settlers, and readers begin to comprehend just how much courage it must have taken to leave everything you know to start a new life on "the frontier" of a young country.
All that said, the book undoubtedly has flaws. The first of these is the relatively limited scope of the book. While the book ostensibly is about the pioneers of the Northwest Territory in general, for the most part, all of the book stays in Ohio (and usually in Marietta). This isn't bad per se, but might come as a surprise to readers.
Of greater concern though for me with this book was how it handles the story of the Native people's inhabiting Ohio. While the book does mention the violence which took place between Natives and American settlers, never does it inhabit the perspective of anyone from the Native side in any meaningful way. I understand that that wasn't what the book was primarily about; still, the almost complete absence of Native perspectives felt like a gaping hole in the book. To be clear, that doesn't mean the book is without merit, only that it tells an incomplete story.
Bottom line: The Pioneers is a worthy read for fans of American history, but probably will require additional reading to get a full perspective on the events being depicted.