Ward's novel is divided into twelve chapters, each corresponding with a day either preceding, during, or following the strike of Hurricane Katrina. Esch, a 15-year-old girl living in the fictional Bois Sauvage, Mississippi, is the novel's first-person narrator.
Esch begins the novel witnessing the dog China giving birth to a litter of puppies. China belongs to Skeetah, Esch's 16-year-old brother, who treasures China like other men treasure the loves of their lives. Outside the shed where China gives birth, Esch's father, to whom she refers as Daddy, hammers plywood onto every conceivable surface. He has just learned of a bad hurricane approaching the Gulf Coast, and he is hell-bent on preparing for it.
Esch's brothers, however, are not concerned by Daddy's warnings. Randall, Esch's 17-year-old brother, plays basketball with his friends, and her younger brother, Junior, hides under their porch. Esch's mother, to whom she refers as Mama, died giving birth to Junior seven years ago, leaving Esch to navigate a testosterone-fueled environment.
Randall's friends, including his closest friend, Manny, often play basketball on the family's property, called the Pit. Manny and Esch occasionally sneak away to have passionate yet unromantic sex, and Esch is concerned that she might be pregnant with his child. Although Esch is no stranger to sex, having lost her virginity a few years ago to Skeetah's friend, Marquise, she feels that sex with Manny is different from her past affairs. She loves him and often compares herself and Manny to Medea and Jason, the Greek mythological couple infamous for betrayal and revenge.
China gives birth to a litter of puppies, with only one stillborn. When Esch, Skeetah, and his friend, Big Henry—named so for his large frame—make a trip to the grocery store for dog food, Esch steals a pregnancy test and uses it when she arrives back home. The test reads positive. At fifteen years old, Esch is pregnant with Manny's child.
In the days that follow, Esch constantly battles morning sickness. Likewise, one of China's puppies comes down with Parvovirus, and Skeetah formulates a plan to steal worm medicine from their white neighbors' barn. In the meantime, Skeetah kills the infected puppy to prevent the virus from spreading, and then jumps into the rancid water in the lake behind his house to wash clean. There, Esch makes a move on Manny that he rebuffs, making clear that he envisions their fling as purely sexual and not romantic.
On a mission to steal the worm medicine that he needs to cleanse China and her litter of the virus, Skeetah and his siblings are caught by the white family and chased by their dog. China wins a fight against the dog, and Skeetah administers the medicine to China and her puppies. Days later, however, the medicine seems to have worsened the dogs' health, and China lashes out by killing the puppy that most strongly resembled the dog that impregnated her, Kilo. Daddy grows frustrated at the amount of energy Skeetah is devoting to China instead of helping him prepare for the storm.
Growing ever more concerned about the storm, Daddy begins tearing down the family's chicken coop down to use as plywood, asking Randall to drive the tractor into the coop on his signal. Misinterpreting Daddy's directions, Randall drives forward at the wrong time, catching Daddy's hand in the tractor's grill and causing him to lose fingers. From then on, Daddy is unable to prepare the property for the hurricane, which he learns is called Katrina.
Esch and her brothers attend Randall's basketball game, where Esch spots Manny and his girlfriend, Shaliyah. When Esch escapes to use the bathroom, Manny follows her and they have sex until he realizes that she is pregnant and flees. Esch is heartbroken, which Skeetah notices when she returns to watch the game. Skeetah picks a fight with Manny and his cousin, Rico, who challenges Skeetah to a dogfight between China and Kilo. Although he knows it will be risky for China to fight while still nursing her litter, Skeetah agrees.
Skeetah pits China, who is still weak from illness, against Kilo in the final round of the dogfight. Although Kilo attacks her vulnerable breasts, still full of milk, China summons the anger that Esch imagines she bears towards Kilo and sinks her teeth into his neck, victorious.
As the kids take over Daddy's storm preparation duties, Esch confronts Manny. She informs Manny that he is the father of her child, which he denies. Esch responds by physically attacking him, taking a page from China's fight with Kilo. Afterward, Esch is distraught, but Randall forces her to help him steal food from the white neighbors' house, which he assumes is abandoned. Indeed, the white people are gone, but there is also no food in sight at their house, and Skeetah uses much of the family's money to buy dog food.
The family settles in to wait out the storm. A tree falls through Daddy's room, and Esch believes that China somehow predicted it. Later, the family notices the water flooding the house and moves upstairs. The water, however, moves more quickly than they anticipate, forcing them to swim to the nearby house, which belonged to Esch's grandparents and sits at the top of a hill where it will likely be safe from flooding.
Grabbing hold of a tree trunk, the family makes their way to the house through the storm. Along the way, Skeetah tells Daddy that Esch is pregnant, and Daddy pushes Esch off the trunk, causing her to drop China's puppies into the flood. Skeetah helps Esch find her way back to the trunk as the family approaches the safe house, but his rescue attempt causes China to come loose from the harness he used to secure the dog to his chest. China floats away, and Skeetah is consumed by grief.
As the storm calms the following day, Skeetah sets up camp to await China's return, confident that she was strong enough to survive the hurricane. The rest of Esch's family seeks shelter with Big Henry, who later vows to be there for Esch and her child. Daddy, too, comes around, promising to take Esch to a doctor to ensure her baby's health. Surveying the unprecedented destruction of her community, Esch and her brothers return to their house and await China by Skeetah's side.