Wealthy Minnesotan building-contractor Edgar Freemantle barely survives a severe work-site accident wherein his truck is crushed by a crane. Freemantle loses his right arm, and suffers severe head injuries impairing his speech, vision, and memory. During his long recovery, Edgar experiences suicidal thoughts and violent abusive mood swings, spurring his wife to file for divorce.

On the advice of his psychologist, Dr. Kamen, Edgar relocates southward, renting a beach house on the island of Duma Key, off Florida's coast. Kamen further advises Freemantle to rekindle his onetime sketching hobby as a restorative. Edgar retains local college student Jack Cantori as part-time shopper and personal assistant; soon after, Freemantle meets and befriends the island's other full-time residents, octogenarian heiress Elizabeth Eastlake (sufferer of final-stage dementia, whose family trust owns most of the island), and her live-in attendant, Jerome Wireman, himself a once-gifted attorney whose wife and daughter's tragic deaths led him to (unsuccessfully) attempt suicide via gunshot wound.

Decades-old paranormal phenomena revisit the island as Freemantle delves obsessively into his art. Edgar creates with furious energy, lapsing into a semi-conscious haze; his paintings and sketches capture psychic visions, revealing his ex-wife's romantic affair, his friend's suicidal depression, and his younger daughter Ilse's fleeting marital engagement. Later, Freemantle uses his newfound artistic powers to manipulate the outside world, healing Wireman's degenerating neurological condition, and suffocating a child murderer in his jail cell. During Ilse's visit to Duma Key, the father-daughter duo drive to a disused, overgrown section of the island, where colors seem unnaturally vivid, and Ilse becomes violently ill. Elizabeth Eastlake warns Edgar via telephone conversations that Duma "has never been a lucky place for daughters," and that his paintings should be sold to multiple geographically-distant buyers, lest their otherworldly power grow too concentrated or dangerous.

Freemantle comes to learn that Duma Key's beach house has hosted many successful artists (including Salvador Dalí) during its eighty-year tenure, that Elizabeth Eastlake was, herself, a prodigious artist in her childhood, and that both Edgar and Wireman manifest pronounced psychic talents while on or near the island, seemingly stemming from their debilitating brain injuries. Freemantle's artworks become more vivid and distressing, featuring ship-and-seaside compositions whose vessel and mysterious red-cloaked passenger draw nearer to shore in each successive painting. Elizabeth grows alternately lucid then incoherent as her dementia worsens, scattering her beloved china figurines, murmuring that "The table is leaking," and repeatedly urging Wireman to throw one faceless figurine into her koi pond. In a moment of chilling clarity, Eastlake asks Edgar if he has begun painting the ship yet.

Freemantle's paintings attract statewide acclaim. He hosts an art exhibition and accompanying lecture at an upscale Sarasota gallery, gaining a devoted audience (including Edgar's visiting loved ones) and yielding half a million in sales. Elizabeth Eastlake makes a rare appearance at said exhibition; upon seeing Edgar's ship-and-seaside paintings, she reacts violently, making cryptic references to her childhood playthings and long-drowned sisters, warning that "She has grown so strong," "The table is leaking," and "Drown her back to sleep," before suffering an incapacitating (and ultimately fatal) stroke. Freemantle notices previously-unseen details in his work: the ship's rotting sails, the child-toys littering its decks, screaming faces hiding in its foamy wake.

Narrative timelines interweave as Edgar Freemantle's present-day nightmare parallels the 1927 Eastlake familial tragedy. Young Elizabeth, head-wounded in a childhood horse-carriage accident, turns to sketching and scribbling as a means of recuperation. An outside presence -- "Perse"—speaks to Elizabeth, sometimes in her mind, sometimes through her rag-doll, filling her with knowledge, and reality-altering powers, and a gradual infiltration of sinister urges. Elizabeth directs her bootlegger father to a pile of ship-debris in the shallows, unearthing a red-cloaked porcelain figurine. The girl's sketches grow progressively more alien and malevolent, until, driven by fear, she rebels against Perse, provoking the entity's wrath, after which Elizabeth's twin sisters are lured into the ocean to drown. Only Elizabeth's nursemaid, Melda, takes direct action; as Perse's drowned-sister-things move beachward, the governess holds them off by means of silver jewelry, buying precious moments with her life while Elizabeth neutralizes the Perse-statuette.

Freemantle faces similar otherworldly dangers while unraveling the Eastlake mystery. He returns home to find "Where our sister?" childishly scrawled on an unused canvas. Edgar then discovers that those in possession of his artworks either die, or are possessed and driven to murderous deeds by "Perse." He persuades his loved ones to discard their paintings, but not before a co-opted art critic drowns his daughter Ilse. As Edgar, Jack, and Wireman race to discover the secret of mad Persephone's rise and subsequent banishment, the ghost ship's undead passengers return for them. Fighting their way to the island's overgrown region—Heron's Roost, the original Eastlake manor—the trio locate the Perse-carving, trapped in fresh (as opposed to her native salt) water, and sealed in a (water-filled) ceramic keg of table whiskey, in which a crack has formed during the passage of years ("the table is leaking"). Edgar returns the figurine to fresh-water slumber, and faces down one final Perse-temptation, wearing the face of his drowned daughter Ilse. Freemantle and Wireman then fly north, to Minnesota, where they drop the statuette into Lake Phalen's freshwater depths, to sleep undisturbed.

Edgar Freemantle then commences his final painting: a massive tropical storm, destroying Duma Key.