In 2011, Karen Russell cast a spell over readers with her uncanny debut novel, “Swamplandia!” She wasn’t kidding about that exclamation point. The story involves a plucky 13-year-old girl determined to revive her family’s alligator park.

“Swamplandia!” went on to become a finalist for the Pulitzer Prize in fiction. That year, Russell’s novel was up against an unfinished manuscript by an author who’d died in 2008 and a revised version of a novella published in the Paris Review almost a decade earlier. Historically speaking, being above ground with a new, finished novel has been a great advantage when it comes to winning a Pulitzer. But, alas, that year, in its inscrutable wisdom, the Pulitzer board decided not to give a prize for fiction.

What might have been?

“The Antidote” by Karen Russell. Knopf, 419 pages. $30

The question of possibilities both forgotten and denied snakes through Russell’s second novel, a tempest of a tale called “The Antidote.” Her signature conceits gather again in these pages — a determined girl, a tincture of wizardry, a slash of violence — but this story is dazzlingly original and ambitious. Hovering in the atmosphere somewhere between Colson Whitehead’s “Underground Railroad” and Susanna Clarke’s “Jonathan Strange & Mr Norrell,” “The Antidote” is a historical novel pumped full of just enough magic to make it rise without bursting the bubble of our credulity.

“It fell across our city like a curtain of black rolled down,/ We thought it was our judgment, we thought it was our doom.”

So sang Woody Guthrie about the cataclysmal dust storm that struck on April 14, 1935. On Black Sunday, as the disaster has since been known, a blizzard of dirt churned across America’s desiccated plains, destroying farms, burying homes and plunging the nation further into economic depression.

“The Antidote” opens in the howling wind of that Black Sunday. One of the book’s narrators, Antonina, is locked in a jail cell in a Nebraska town called Uz. You don’t need to catch the allusion to Job’s homeland to know this is a place being severely tested. “I woke up,” Antonina says, “to a sound like a freight train tunneling through me. An earsplitting howl that seemed to shake the stone walls. My body trembled like a husk on the cot. My fingers clawed into the mattress. For those early moments in the dark I was nothing but the fear of floating off.”

Antonina survives the storm but suffers a peculiar sort of bankruptcy. For years, she’s worked as a “prairie witch” who calls herself “the Antidote.” People seek her out to store their memories, either to keep them protected for later or to unburden themselves of experiences they’d rather not carry in their own brains. She’s a human vault of cherished moments, important recollections and unspeakable traumas. Despite how fantastical this sounds, Russell describes the prairie witch as merely a mental bank teller who issues deposit slips and promises security. Like other parts of “The Antidote,” Antonina’s occupation exists along the porous boundary between fable and history that makes the novel such a heady delight.

The crooked sheriff in town sometimes forces Antonina to extract memories from the minds of criminals or witnesses, which is how she ended up in jail on Black Sunday, an inconvenience that may have saved her life. But unfortunately, the dust storm that tore through Uz seems to have blown away all her clients’ mental deposits — 15 years’ worth. She can’t retrieve any of them from the safe of her mind, and when her clients come to make a withdrawal and discover that their secrets have vanished, Antonina knows she’s likely to suffer the unpleasant fate of so many witches.

For a while, it’s difficult to divine the organization of “The Antidote,” which picks up narrators and storylines like a tornado sucks up tires and cows. But give it some room, and the novel’s awesome movement becomes captivating. One of those narrators is a lonely high school girl named Dell, who breathes only for basketball. After her mother was murdered by a serial killer, Dell moved in with her uncle, whose farm is mysteriously thriving amid the drought that’s withering every other crop in town. A skeptic tells Dell, “Nobody will ever pay a nickel to watch girls play ball,” but she won’t give up — not when the heat makes it impossible to practice, or when she should have been helping her uncle, or even when the dust buries their court.

But when her basketball team needs money to attend a championship, Dell is stumped … until she apprentices herself with the Antidote, who makes a particularly gruff boss. Together the prairie witch and the high school girl manage to keep their memory business going without anyone realizing the vault is empty. Of course, this is about as stable as operating a bank that’s dropping depositors’ money down a well, but as so many legendary Wall Street financiers can attest, that practice can be profitable for a while.

This is all charming, but what’s wondrous about “The Antidote” is how implacably it keeps swelling, gathering up swaths of history. In some sections, we’re drawn into a brutal institution for unwed mothers, which allows Russell to examine the way sexual roles were proscribed and enforced to control young women. We learn about Polish peasants who escaped oppression in Europe to settle in Nebraska, Native Americans who were removed from this land to make room for White farmers, and the agricultural malpractice that contributed to the Dust Bowl.

Another fascinating thread follows Cleo, a Black photographer, who’s sent by the federal Resettlement Administration to document farm life during the Depression. Cleo’s work is its own kind of memory-storing, perhaps not so different from the prairie witch’s practice. When Cleo stops in Uz and begins sending back evocative photographs of integrated rural schoolhouses and sporting events, her boss reminds her that diversity is the last thing racist leaders in D.C. want to see. (The more things change …) And when her camera begins revealing images of the land from other eras and alternative timelines, the truly radical ambition of “The Antidote” begins to resolve into clarity like an image in the darkroom.

Russell may be writing about a tiny town in the middle of nowhere, but the scale here is large. Into this book she’s packed a whiff of Steinbeck’s grandeur, a murder mystery, the legacy of genocide, a young woman’s coming of age, a Dickensian story of a missing baby, a warning about climate change and even a talking cat. With all these strange, momentous incidents, “The Antidote” rises into a western epic that grasps for the whole history of White settlement. In the lives of this eccentric cast of characters, her story illuminates how the abuse of the Native peoples and destruction of the environment are intricately woven together in the deadly charade known as Manifest Destiny.

“When many thousands of us decide to forget the same truths, what happens?” Dell’s uncle asks. “Look at what is happening to the soil without roots. We are the children of these crimes of memory, and we go on committing them.”

Across the vast canvas of this novel, Russell aims for nothing less than a consideration of the role that intentional amnesia plays in American history and American life. To embark on the adventure of reading “The Antidote” is to place yourself under the enchanting and challenging care of a writer who is guilty of actual witchcraft.