In 1985, Rose Daniels, four months pregnant, sat in her living room after her husband Norman, a police detective, punched her three times in the abdomen, causing her to miscarry. Norman wiped up the blood, carried Rose to the foot of the stairs to stage the scene, and coached her to tell paramedics she fell. Rose retreated into a dissociative state and remained trapped in Norman's abuse for nine more years, totaling fourteen years of marriage.
The main narrative begins when Rose discovers a single drop of blood on the bedsheet from a nosebleed Norman caused the night before. This small detail awakens her from years of numbness. Sitting in her bentwood rocker, she catalogs a decade of abuse: bite marks, broken ribs, the miscarriage, kidney damage from repeated blows. An internal voice urges her to stay, but a deeper voice warns that Norman may leave her permanently maimed rather than kill her. Rose takes Norman's ATM card, grabs her purse, and walks out the front door.
She flees by taxi and bus, withdrawing $350 before boarding a Continental Express headed approximately eight hundred miles away. In the cab, she resolves to reclaim her maiden name, Rosie McClendon. She buys her ticket under a false name, pays cash, and drops the ATM card into a trash barrel. A small-time criminal named Ramon Sanders retrieves it.
Rosie arrives at a large midwestern bus terminal at three in the morning. A Travelers Aid volunteer named Peter Slowik refers her to Daughters and Sisters (D&S), a privately endowed domestic violence shelter. Inside, she meets Anna Stevenson, the director, who offers her a bed for up to eight weeks and a chambermaid job at the Whitestone Hotel. Rosie bonds with Pam Haverford, a fellow resident and hotel coworker who becomes her closest friend. She also learns self-defense from Gert Kinshaw, who teaches informally at the shelter. Over a month, her chronic back pain improves and she begins experiencing small pleasures that feel revelatory after years of isolation.
Meanwhile, Norman uses his detective skills to hunt for Rose. He brutalizes Ramon to extract information and eventually identifies the correct city after learning Rose asked for a bus by departure time rather than destination, indicating she wanted to get as far away as possible.
Rosie visits a pawnshop to sell her engagement ring and discovers it contains a zirconia, not a diamond. She trades the fake ring for an oil painting that seizes her attention: It depicts a blonde woman in a chiton, an ancient draped gown, of a reddish-purple color called rose madder, standing atop an overgrown hill above the ruins of a temple. Outside, an elderly audiobook producer named Rob Lefferts hears Rosie read aloud from a paperback and, astonished by her natural talent, offers her a job recording audiobooks. Bill Steiner, the young pawnshop jeweler, watches Rosie leave with quiet fascination.
Rosie moves into a room at 897 Trenton Street and hangs the painting beside her window. Soon the painting seems to reveal more of its world each time she looks, and she discovers debris behind its backing that matches the flora in the image. Bill tracks down her address, takes her to dinner, and asks her for a Saturday date: a motorcycle ride to a lakeside spot, followed by the D&S benefit concert. That evening, Anna calls with alarming news: Peter Slowik has been murdered, bitten over three dozen times. Anna suspects Norman because Rosie described him as "a biter" in group therapy. Rosie panics, certain Norman has arrived in the city.
Norman discovers a flier for the D&S picnic at Ettinger's Pier and constructs an elaborate disguise, shaving his head and posing in a secondhand wheelchair as a paralyzed biker sympathizer. Meanwhile, Rosie reconciles with Bill and tells him the full story of her marriage. Bill asks whether Norman might have murdered Wendy Yarrow, a woman whose civil suit had threatened Norman's career, a question Rosie immediately recognizes as plausible.
That night, Rosie steps through the painting onto a moonlit hilltop above a ruined structure called the Temple of the Bull. She encounters Rose Madder, whose back is always turned and whose voice is sweet but insane. Rose Madder commands Rosie to descend into a labyrinth called the Maze and retrieve her baby, promising: "I repay." Rosie navigates the maze using seeds from a lone pomegranate tree as trail markers, evading a blind bull called the Erinyes by throwing a blood-scented decoy stone, and returns the infant to Rose Madder. Rose Madder gives Rosie a gold armlet, and Rosie wakes in her room the next morning with the armlet under her bed.
On Saturday, Bill takes Rosie to Shoreland, a lakeside picnic area. He shows her a vixen nursing cubs beneath a fallen tree and tells her he loves her. At Ettinger's Pier, Norman infiltrates the D&S picnic in his wheelchair disguise. When Rosie fails to appear, he ambushes Cynthia Smith, a shelter resident, beating her and demanding Rosie's location. Gert discovers the assault and fights Norman, flipping him and wresting away his taser. Norman flees wearing a stolen rubber bull mask.
Norman's psychosis deepens. He corners Pam in a hotel housekeeping room and kills her, then uses information from her locker to break into the D&S building and find Rosie's address. He murders Anna and the two police officers stationed outside Rosie's building. When Rosie and Bill arrive, Norman attacks in the darkened vestibule, choking Bill and shooting an upstairs neighbor who intervenes. Rosie discovers extraordinary strength, dislocating Norman's jaw, and drags Bill into her room, where the closet has become a portal into the painting's world.
Inside, Rosie dons the rose madder chiton and lures Norman through the temple. Norman's rubber bull mask has fused to his face, and he pursues her through dead gardens and across a black stream. Rose Madder waits in a clearing disguised as Rosie. When Norman seizes her shoulder, Rose Madder turns to reveal a monstrous visage and destroys him, seeding his corpse with pomegranate seeds. Dorcas, Rose Madder's attendant, gives Rosie a bottle of water from a stream of forgetfulness. Rose Madder seizes the gold armlet back, and Rosie pulls Bill through the portal, which closes permanently. She gives Bill a drop of the water to dissolve his memories and tells the police that Norman broke in and fled.
Rosie incinerates the painting, marries Bill, and builds a new life recording audiobooks and raising a daughter named Pamela Gertrude. She discovers, however, that she has inherited episodes of terrifying rage from her encounter with Rose Madder. She channels this fury into batting cages, but the voice of Rose Madder whispers inside her: "I repay." Recognizing the rages are connected to the pomegranate tree, Rosie drives to Shoreland and buries the last seed, circled by Norman's Police Academy ring, at the base of the fallen tree where the fox den once was. Over the following years, a tree grows from that spot, producing buds of rose madder color. Rosie visits every spring, and the rages depart. The novel closes with Rosie singing a Carole King and Maurice Sendak song, "I'm really Rosie, and I'm Rosie Real," as the old vixen stands at the clearing's edge, listening.