Focusing on the effects of the American Revolution on the frontiers of Spanish Louisiana and British West Florida, Independence Lost incorporates biographies of eight individual historical figures alongside more general analysis of the Gulf Coast during the 18th and early 19th centuries.

Academic reviews of the book were positive, praising DuVal's focus on a region typically ignored by histories of the Revolution, alongside the work's character narratives and vivid description of period warfare.

Alongside another chapter expanding on the recent geopolitics, Part I ("The Place and Its People") branches into separate introductions to each of the main "characters" of the book, although married couples are covered at once – Oliver Pollock with Margaret O'Brien, as well as James Bruce with Isabella Chrystie.

Part III ("The Revolutionary War") takes place over the Gulf Coast campaign and the height of Spanish conflict with British forces in North America, culminating in the 1781 Siege of Pensacola.

A conclusion chapter serves as an epilogue, describing the achievement and effects of American hegemony along the Gulf Coast through the Louisiana Purchase and the War of 1812.Eight historical figures, introduced by DuVal as the book's "characters",[9][10] are detailed throughout the text.

The book drew scholarly comparison to Alan Taylor's 2016 American Revolutions due to their shared focus on transnational and Continental history, albeit with Independence Lost taking a narrower geographical scope.

[23] Continental history has been critiqued for its broadness and ill-defined motivations and form, with historian Brendan McConville describing the school as comprising "at least five types", ranging from focuses on the border regions effects on the Thirteen Colonies and the Revolution, to centering geographical and biological factors across the North American continent.