In 2006, a survey of eminent authors and critics conducted by The New York Times named Underworld as the runner-up for the best work of American fiction of the past 25 years, behind only Toni Morrison's Beloved.

[6] The prologue is a fictionalized account of The Shot Heard 'Round the World, a home run by Bobby Thomson on October 3, 1951, that won the National League pennant for the New York Giants against their cross-town rivals, the Brooklyn Dodgers.

In DeLillo's account, the game-winning ball is caught by a young black fan named Cotter Martin, while J. Edgar Hoover, watching in the stands, is informed in the middle of the game of the first Soviet test of the hydrogen bomb.

The remainder of the novel, comprising six parts and an epilogue, is a reverse chronological account of the life of Nick Shay, the man who ultimately ends up with the baseball, from his undirected existence as an executive of a waste management company in Arizona in the 1990s back to his childhood in the Bronx in the 1950s, though the non-linear narrative includes a large number of digressions and ancillary subplots.

Elsewhere, in the Bronx, a pessimistic, germophobic nun named Sister Edgar, who was Nick Shay's Catholic school teacher in the 1950s, works among the unbelieving poor and sick.

In Part 3, in the spring of 1978, Nick attends a waste management conference in the Mojave Desert and meets a swinger named Donna, while Marvin Lundy traces the baseball to San Francisco.

Part 4, in the summer of 1974, mainly concerns Klara Sax, who is working as an artist in New York City, and Matt Shay, Nick's brother, a former chess prodigy, who is a scientist in the nuclear weapons program in New Mexico.

In another flashback, Cotter Martin's father sells his baseball to Charles Wainright, a white fan standing in line with his son outside of Yankee Stadium.

Part 6, from the fall of 1951 to the summer of 1952, relates how Nick Shay, running loose after his father left his family, accidentally kills his friend George Manza.

[11]He also remarked on the phonetics of the novel, telling Delillo "you use these Saxonic devices heavily and over and over and yet the prose never seems heavy or straining; in fact just the opposite: it always seems exquisitely controlled, sober, poised rather than lunging.

[2] The literary critic Harold Bloom, although also expressing reservations about the book's length, said Underworld was "the culmination of what [DeLillo] can do" and one of the few contemporary American works of fiction that "touched what I would call the sublime," along with works by Cormac McCarthy (Blood Meridian), Philip Roth (American Pastoral and Sabbath's Theater), and Thomas Pynchon (Mason & Dixon, Gravity's Rainbow and The Crying of Lot 49).

"Better Things for Better Living Through Chemistry" was an advertising slogan for DuPont, while "The Cloud of Unknowing" is an anonymous work of Christian mysticism written in Middle English in the latter half of the 14th century.

The book also employs Lenny Bruce’s reaction to the Cuban Missile Crisis and Soviet Union's atomic weapons program (including their testing grounds in Kazakhstan).