According to Daniel Aaron in American Heritage, the publication of U.S.A. "secured John Dos Passos's place in American literary history." However, Aaron remarked, eventually his reputation "faded, and his rowdy, acrid masterpiece petrified into a 'classic.' " Despite this, Aaron noted, "no other novelist of his times had so ingeniously evoked the scope and variety of the United States."

Many critics have commented on the book's pessimistic nature, but most have found this pessimism a necessary part of Dos Passos's style and message. Perry D. Westbrook wrote in the Reference Guide to American Literature that the book is "disheartening," remarking that:

[The book] inevitably leaves the reader with the sense
of profound loss, a feeling of ideals and values betrayed.
Yet the fervor with which Dos Passos wrote
indicates that he believes the loss might not be irretrievable.
He wrote from imagination and outrage...