Reiss was born in 1964 and lived as a very young boy lived in Washington Heights, an area of New York City populated then by mostly German-speaking immigrant families. He grew up in Texas and Massachusetts and before becoming a journalist had various jobs including bartender, security guard, elementary school teacher and producer of industrial videos.

Reiss' first major book, was Führer-Ex; Memoirs of a Former Neo-Nazi, published in 1996 by Random House. Written with Ingo Hasselbach, it was the first inside exposé of the European neo-Nazi movement. It first appeared as a 21,000 word excerpt in The New Yorker.

Reiss is best known as the author of The Orientalist, a biography of Lev Nussimbaum, a Jew who transformed himself into a Muslim prince in Germany during the Holocaust. Part history, part cultural biography, and part literary mystery, it tells the story of how Lev Nussimbaum escaped the Russian Revolution in a camel caravan and, as "Essad Bey" and "Kurban Said," became a celebrated adventurer and author of the enduring novel Ali and Nino-—a story of love across ethnic and religious boundaries, published on the eve of the Holocaust—is still in print today.

But Lev’s life grew wilder than his wildest stories. He married an international heiress who had no idea of his true identity—until she divorced him in a tabloid scandal. His closest friend in New York, George Sylvester Viereck—also a friend of both Freud’s and Einstein’s—was arrested as the leading Nazi agent in the United States. Lev was invited to be Mussolini’s official biographer—until the Fascists discovered his true origins. Under house arrest in the Amalfi cliff town of Positano, Lev wrote his last book—scrawled in tiny print in half a dozen notebooks never before read by anyone—helped by a mysterious half-German salon hostess, an Algerian weapons-smuggler, and the poet Ezra Pound.

Reiss, himself Jewish, was drawn to write The Orientalist, partially based on his own grandparents' experience. To research the book he traveled to 10 countries, from Baku to Berlin to Hollywood, and published his initial investigation in The New Yorker. He spent five years tracking down secret police records, love letters, diaries, and the deathbed notebooks. Beginning with a yearlong investigation for The New Yorker, he pursued Lev’s story across ten countries and found himself caught up in encounters as dramatic and surreal, and sometimes as heartbreaking, as his subject’s life. Reiss’s quest for the truth buffets him from one weird character to the next: from the last heir of the Ottoman throne to a rock opera-composing baroness in an Austrian castle to an aging starlet in a Hollywood bungalow full of cats and turtles.

The Orientalist appeared on many "top ten" of the year lists and was shortlisted for the 2006 Samuel Johnson Prize for best nonfiction book in the English language. It has been published in 15 other languages and is still appearing in others. It has been declared one of the best books of the year in various countries where it appears.

Reiss is currently writing a biography of General Thomas-Alexandre Dumas, the son of a Haitian slave who rose to become one of the greatest swordsmen and generals in France.