Helprin was raised on the Hudson River and in the British West Indies, and holds degrees from Harvard College and Harvard's Graduate School of Arts and Sciences. His postgraduate work was done at Princeton University and the University of Oxford. He served in the British Merchant Navy, the Israeli infantry, and the Israeli Air Force.

His first novel, published in 1977, was Refiner’s Fire: The Life and Adventures of Marshall Pearl, a Foundling. Winter’s Tale (1983) is a sometimes fantastic tale of early 20th century life in New York City. In 1991, he published A Soldier of the Great War. Memoir from Antproof Case, published in 1995, includes long comic diatribes against the effects of coffee. Helprin came out with Freddy and Fredericka, a satire, in 2005.

Helprin has published three books of short stories: A Dove of the East & Other Stories (1975), Ellis Island & Other Stories (1981), and The Pacific and Other Stories (2004). He has also written three children’s books, all of which are illustrated by Chris Van Allsburg: Swan Lake, A City in Winter, and The Veil of Snows. His works have been translated into more than a dozen languages.

Helprin's writing has appeared in The New Yorker for two decades. He writes essays and a column for the Claremont Review of Books. His writings, including political op-eds, have also appeared in The Wall Street Journal (for which he was a contributing editor until 2006), The New York Times, The Washington Post, the Los Angeles Times, The Atlantic Monthly, The New Criterion, National Review, American Heritage, and other publications.

On May 20, 2007, Helprin published an op-ed for The New York Times that argued that intellectual property rights should be assigned to an author or artist as far as Congress could practically extend it. The overwhelmingly negative response to his position on the blogosphere and elsewhere was reported on The New York Timess blog the next day. Helprin himself was said to be shocked by the response.

In April 2009, HarperCollins published Helprin's "writer's manifesto", Digital Barbarism. In May, Lawrence Lessig penned a review of the book entitled The Solipsist and the Internet in which he described the book as a response to the "digital putdown" heaped upon Helprin's New York Times op-ed. Lessig called Helprin's writing "insanely sloppy" and also criticized HarperCollins for publishing a book "riddled with the most basic errors of fact."

In response to such criticisms Helprin wrote a long defense of his book in the September 21, 2009 edition of National Review, which concluded: "Digital Barbarism is not as much a defense of copyright as it is an attack upon a distortion of culture that has become a false savior in an age of many false saviors. Despite its lack of mechanical perfections, humanity, as stumbling and awkward as it is, is far superior to the machine. It always has been and always will be, and this conviction must never be surrendered. But surrender these days is incremental, seems painless, and comes so quietly that warnings are drowned in silence."

In May 2010, Helprin wrote an article which stated that China's military is "on the cusp" of being able to dominate Taiwan and the rest of the Far East.

A Fellow of the American Academy in Rome and a former Guggenheim Fellow, Helprin has been awarded the National Jewish Book Award and the Prix de Rome from the American Academy and Institute of Arts and Letters.

He is also a senior fellow at the Claremont Institute for the Study of Statesmanship and Political Philosophy. In 1996 he served as a foreign policy advisor and speechwriter to presidential candidate Bob Dole.

In May 2006, the New York Times Book Review published a list of American novels, compiled from the responses to "a short letter [from the review] to a couple of hundred prominent writers, critics, editors and other literary sages, asking them to please identify 'the single best work of American fiction published in the last 25 years.'" Among the twenty-two books to have received multiple votes was Helprin's Winter's Tale.

In 2006 Helprin was awarded the Tulsa Library Trust's Peggy V. Helmerich Distinguished Author Award.