In the fictional narrative sections, the U.S.A. trilogy relates the lives of twelve characters as they struggle to find a place in American society during the early part of the 20th century.

"The Camera Eye" sections are written in stream of consciousness and are an autobiographical Künstlerroman of Dos Passos, tracing the author's development from a child to a politically committed writer.

Camera Eye 50 contains the arguably most famous line of the trilogy, when Dos Passos states upon the executions of Sacco and Vanzetti: "all right we are two nations."

[2] Stanley Corkin has specifically expostulated The 42nd Parallel in the context of readings of Hegelian Marxism with respect to the particular historical time of the novel.

The first and last newsreels in each of the three books within U.S.A. tend to mirror each other, for instance, The 42nd Parallel begins with declarations that the 20th century will be shaped by America and its territorial expansion, juxtaposed to British struggles in the Boer War and dead soldiers in the Philippines.

Dos Passos portrays the everyday situations of the characters before, during, and after World War I, with special attention to the social and economic forces that drive them.

Dos Passos does not show much sympathy for upwardly mobile characters who succeed, but is always sympathetic to the down and out victims of capitalist society.

The book expresses an obvious animosity to President Woodrow Wilson, depicting in detail his suppression of internal dissent during and immediately after World War I.

Dos Passos added a prologue with the title "U.S.A." to The Modern Library edition of The 42nd Parallel and the same plates were used by Harcourt Brace for the trilogy.

[11]: 1256  The first illustrated edition was limited to 365 copies, 350 signed by both Dos Passos and Marsh in a deluxe binding with leather labels and beveled boards.