When Sarah McNally, the owner of McNally Jackson bookstore in Lower Manhattan, set out to open a second location, she went to a neighborhood with a sterling literary reputation, the home turf of writers from Edgar Allan Poe to Nora Ephron: the Upper West Side.

She was stopped by the skyscraper-high rents.

“They were unsustainable,” Ms. McNally said. “Small spaces for $40,000 or more each month. It was so disheartening.”

Rising rents in Manhattan have forced out many retailers, from pizza joints to flower shops. But the rapidly escalating cost of doing business there is also driving out bookstores, threatening the city’s sense of self as the center of the literary universe, the home of the publishing industry and a place that lures and nurtures authors and avid readers.

“Sometimes I feel as if I’m working in a field that’s disappearing right under my feet,” said the biographer and historian Robert Caro, who is a lifelong New Yorker.