Set in the rugged Ozark Mountains of Missouri during the Prohibition era (1920–1933, when the manufacture and sale of alcohol was banned nationwide), the novel follows three generations of the Strong family as they fight to survive through moonshining, loss, and the fierce bonds of sisterhood.
In October 1912, Lidy Strong, a medicine woman who serves as healer and midwife for her remote mountain community, faces a crisis. Her daughter-in-law, Alta, lies comatose after deliberately jumping from a barn loft to end her pregnancy. Lidy moves in with her son Hiram and his two young daughters, Rebecca and Elsie, determined to keep Alta alive long enough for the baby to survive. She administers cedar berry tea to induce labor and enlists both granddaughters to help with the delivery. The baby, expected to be a boy, turns out to be a girl. Hiram, devastated at first, is transfixed by the tiny, orange-haired infant. He names her Jace, declares she will save the family, and everyone calls her Shine.
Seventeen years later, Shine is a firecracker with a natural gift for distilling. She rouses her hungover father each morning and hikes with him to their hidden still along Kinney Creek, wearing special boots fitted with cow hooves on the soles to disguise her footprints. Rebecca, the eldest sister at 27, handles supply runs to Hanson's General Store, where the proprietor's son, Jedediah Hanson, makes pointed remarks about the family's large sugar purchases. Elsie, the middle sister, is restless for a life beyond the farm. Jed has been courting her, though the family suspects his real interest lies in their moonshine operation.
Federal Prohibition agents John Flanagan and R. J. McConnell arrive in the area. Flanagan, a young idealist from Ohio, was partnered with the flamboyant McConnell in New York, where the duo's undercover busts made them famous before their reassignment to the Ozarks. Acting on a tip, they search the Strong property but are outmaneuvered: quart jars of peach halves in the root cellar are actually soaking in moonshine, hidden in plain sight. The agents leave empty-handed, though Flanagan finds one of Shine's cow-hoofed boots on the trail.
Lidy discovers that Elsie is pregnant and secretly doses her buttermilk with abortifacient herbs, but Elsie intuits the deception and dumps the drinks. Flashbacks reveal two buried secrets: a hidden letter proves that a red-haired traveling preacher named Robert Smythe, not Hiram, is likely Shine's biological father; and Lidy smothered the comatose Alta, ending her life as an act of mercy.
Hiram and Shine are ambushed at the still. McConnell, increasingly erratic from late-stage syphilis, opens fire without provocation, killing Hiram. Flanagan, who did not fire, takes a bullet from Hiram in the shoulder. The sisters pursue the shooters but lose them at the road. Sheriff Burkett refuses to help, telling Shine that moonshiners have no legal recourse.
Shine takes charge. She forces a shotgun wedding between the pregnant Elsie and Jed, with guns displayed and a reluctant pastor officiating. Rebecca holds her peace despite suspecting, from the distinctive sole pattern of Jed's boots, that he led the Prohibition agents to the still. Shine then uses Jed's Ford Model A to drive moonshine to Hot Springs, Arkansas, a lawless resort town. She negotiates an exclusive deal with the Southern Club, the city's premier casino, at 25 dollars per gallon.
The second delivery run ends in disaster. Jed crashes the car on mountain roads, shattering Rebecca's right leg and destroying most of the moonshine. Shine is stranded in Hot Springs, owing money to the club's bar manager, Merle. She takes a bartending job to pay off the debt. Jed, who has squandered the family's earnings on gambling, is sent home under Lidy's supervision. Elsie gives birth to a boy she names Hiram, called Hi.
At a boardinghouse dinner, Shine recognizes Flanagan, who has left Prohibition enforcement and joined the Federal Bureau of Investigation (FBI). She pulls her pistol, but he reveals his bullet wounds, proving he was not the shooter. He tells her the full story: McConnell killed Hiram, and Jed was the informant who led the agents to the still. Shine and Flanagan begin searching Hot Springs for McConnell, their relationship deepening into unspoken attraction. Months later, they find McConnell dead in a hospital morgue, his body ravaged by syphilis. Shine's quest for vengeance collapses. Flanagan kisses her, and she kisses him back before pulling away, insisting they can never be on the same side.
Three years pass. Shine becomes a celebrated bartender, serving regulars including Al Capone, who gives her a business card for a contact in St. Louis. Her friend Birdie, an orphan who works at the club, is gang-raped by associates of fugitive bank robber Frank "Jelly" Nash. Shine places Birdie at the boardinghouse of Bernyce Ward, a kind older woman. Birdie discovers she is pregnant and refuses to end the pregnancy. Meanwhile, Rebecca undergoes months of rehabilitation at Buckstaff Bathhouse, where a Black attendant named Eulalie becomes her caretaker and eventually her lover. Rebecca regains the ability to walk, though with a permanent limp.
On the farm, Lidy suffers a massive stroke, leaving her paralyzed but mentally sharp. She communicates through blinks and begs Elsie to end her life. While searching Lidy's Bible, Elsie discovers the hidden letter about Shine's parentage and resolves that there will be no more secrets. Her marriage has disintegrated: Jed drinks, cheats, and chokes her when confronted, leaving bruises she hides beneath high-necked dresses.
Shine spots Nash in Hot Springs and calls Flanagan at the FBI. He arrests Nash, who is later killed alongside four officers in a botched rescue attempt at Kansas City's Union Station, an event known as the Kansas City Massacre. Flanagan is the sole officer to escape unharmed. When Merle traces the tip-off to the club, Shine disguises herself, escapes through a window, and catches the next train to Missouri.
The three sisters reunite at the farm. When Elsie reveals the bruises on her throat, Shine lures Jed to the barn loft, forces him to write a suicide note, and presents a noose. Jed kicks the stool away, but Rebecca fires her rifle from the loft ladder and severs the rope. Elsie climbs up, takes control, and orders Jed to leave permanently, threatening death if he returns.
During the confrontation, a kerosene lantern Elsie knocked from its nail ignites the cabin. Lidy, paralyzed and alone, experiences the fire as liberation. The sisters find the cabin engulfed and cannot save their grandmother. Neighbors rebuild the home in tribute to Lidy's lifetime of service.
With Prohibition repealed in December 1933, Flanagan arrives at the farm, having quit the FBI after the massacre. He brings Eulalie and a baby named Wren, Birdie's daughter. Birdie died in childbirth, and Bernyce, the boardinghouse owner who briefly cared for the infant, entrusted her to Flanagan to deliver to Shine. Rebecca and Eulalie reunite. Shine accepts the responsibility of raising Wren.
An epilogue set in June 1941 is narrated by eight-year-old Wren as the Flanagan family drives from St. Louis, where Shine runs a tavern, to the Ozark farm. Rebecca and Eulalie live together on the farm. Elsie works at Hanson's store and raises Hi, her son with Jed, with the support of her in-laws. Wren knows Flanagan is not her biological father but treasures him as her daddy, just as Shine treasured Hiram. The novel closes with Wren anticipating the love of the Strong women who shaped her world.