The Road follows an unnamed father and son journeying together across a grim post-apocalyptic landscape, some years after a great, unexplained cataclysm has destroyed civilization and almost all life on Earth. Realizing that they will not survive another winter in their unspecified original location, the father leads the boy south, through a desolate American landscape along a vacant highway, towards the sea, sustained only by the vague hope of finding warmth and more "good guys" like them, and carrying with them only what is on their backs and what will fit into a damaged supermarket cart.

The setting is very cold, dark and filled with ash and the land is devoid of living vegetation. There is frequent rain or snow, and electrical storms are common. Many of the remaining human survivors are cannibalistic gangs or nomads, scavenging the detritus of city and country alike for human flesh, though that too is almost entirely depleted.

Overwhelmed by this desperate and apparently hopeless situation, the boy's mother, pregnant with him at the time of the cataclysm, commits suicide when the boy is about five or six; the rationality and calmness of her act being her last "great gift" to the man and the boy. The father coughs blood every morning and eventually realizes he is dying, yet still struggles to protect his son from the constant threats of attack, exposure, and starvation. The revolver they carry, meant for protection or suicide if necessary, has only one round for the entire story. The boy has been told to use it on himself if capture is imminent, to spare himself the horror of death at the hands of the cannibals.

In the face of these obstacles, the man and the boy have only each other. They repeatedly assure one another that they are "the good guys," who are "carrying the fire." On their journey, the duo scrounge for food, encounter roving bands of cannibals, and contend with horrors such as a newborn infant being roasted on a spit, and people being kept captive as they are slowly harvested for food. The vast majority of the book is written in the third person, with references to "the father" and "the son" or to "the man" and "the boy."

Although the man and the boy eventually reach the sea, neither the climate nor availability of food has improved. The man succumbs to an illness and dies, leaving the boy alone, though not long before he dies, the father tells the boy that he can continue to speak with him in his imagination after he is gone. The boy holds wake over his father's corpse for three days, with no idea of what he is to do next. On the third day, the grieving boy encounters a man who has been tracking the father and son. This man, who has a woman and two children of his own, a boy and a girl, invites him to join his family after convincing the boy that he is indeed one of the "good guys" like the boy and his dead father. A brief epilogue following meditates on nature and infinity in this altered environment.