Born in New York City into a Jewish family that had emigrated from Russia, he earned an A.B. from Columbia University in 1934, where he studied under philosopher Irwin Edman. Soon thereafter, he became a radio scriptwriter, working in David Freedman's "Joke Factory" and later with Fred Allen and in 1941, for the United States government, writing radio spots to sell war bonds.

Wouk joined the United States Navy and served in the Pacific Theater, an experience he later characterized as educational; "I learned about machinery, I learned how men behaved under pressure, and I learned about Americans." Wouk served as an officer aboard two destroyer minesweepers (DMS), the USS Zane and USS Southard, becoming executive officer of the latter. He started writing his first novel, Aurora Dawn, during off-duty hours aboard ship. Wouk sent a copy of the opening chapters to Irwin Edman who quoted a few pages verbatim to a New York editor. The result was a publisher's contract sent to Wouk's ship, then off the coast of Okinawa. The novel was published in 1947 and became a Book of the Month Club main selection. His second novel, City Boy, proved to be a commercial disappointment at the time of its initial publication.

In 1952, after nearly giving up literature as a career, Wouk won the Pulitzer Prize for his novel, The Caine Mutiny (1951). A best-seller drawing from his wartime experiences, The Caine Mutiny was adapted by the author into a Broadway play and later a film, with Humphrey Bogart portraying Lt. Commander Philip Francis Queeg, captain of the DMS Caine.

He married Betty Sarah Brown in 1945, with whom he had three sons, becoming a fulltime writer in 1946 to support his growing family. His first-born son, Abraham Isaac Wouk, died in a tragic accident as a child; Wouk later dedicated War and Remembrance to him with the Biblical words, "He will destroy death forever." His novels after The Caine Mutiny include Marjorie Morningstar (1955), Youngblood Hawke (1962), and Don't Stop the Carnival (1965). In the 1970s, Wouk published his two most ambitious novels, The Winds of War (1971) and War and Remembrance (1978). He described the latter, which included a devastating depiction of the Holocaust, as "the main tale I have to tell."

Wouk hired highly-qualified young historians to assist him with the research for his later historical novels, and their details are highly accurate. Experts have described The Caine Mutiny as one of the best depictions of daily life aboard a US ship during the Second World War.

In 1998, Wouk received the Guardian of Zion Award.

He and Sarah live in Palm Springs, CA.