After serving with the United States Army Air Forces in the China Burma India Theater during World War II, he graduated from Harvard with a bachelor’s degree in 1947; in 1947 and 1948 he attended the Sorbonne, and from 1948 to 1949 the Institut d’Études Politiques de Paris. He then began his career in journalism as Time correspondent in Paris in 1950. After covering Europe, the Middle East, and Africa (where he was North Africa bureau chief in 1958-59), he went to Asia, where he spent the most influential part of his career. He was friends with Anthony Lewis and Bernard Kalb.  He covered Asia from 1959 until 1974 for Time, Life, the Saturday Evening Post, the London Observer, the Washington Post, and NBC News. Present in Vietnam in July 1959 when the first Americans were killed, he reported on the Vietnam War in its entirety. This landed him a place on the master list of Nixon political opponents. It was during this time that he began to write Vietnam: A History (1983).

He was chief correspondent for the 13 hour Vietnam: A Television History series, aired on PBS’s American Experience; it won six Emmy Awards, a Peabody Award, a George Polk Award and an DuPont-Columbia Award. In 1990, Karnow won the Pulitzer Prize for History for his book In Our Image: America’s Empire in the Philippines. His other books include Mao and China: From Revolution to Revolution, which was nominated for a National Book Award; and Paris in the Fifties (1997), a memoir history of his own experiences of living in Paris in the 1950s. He also worked for The New Republic and King Features Syndicate.  Later in life, he tried to write a book on Asians in the United States. A book on Jewish humor progressed only to an outline. He also contemplated a memoir to be titled Interesting times or Out of Asia.

His first marriage ended in divorce. In 1959, he married Annette Kline, an artist who was working at the time as cultural attaché for the U.S. State Department in Algiers. Annette, died of cancer in July 2009. They had a son and a daughter. Karnow belonged to the Council on Foreign Relations and the American Society of Historians. Karnow died on January 27, 2013 at his home in Potomac, Maryland at age 87 of congestive heart failure.