After Germany invaded Poland in 1939, Lemkin escaped to Sweden, where he became a lecturer at the University of Stockholm. Invited to Duke University in North Carolina by law professor Malcolm McDermott, who had earlier met and worked with him in Poland, Lemkin made an arduous journey east through Russia, Siberia, and Japan, arriving on the East coast of the U.S. in 1941 as a refugee.

Soon after America entered the war, the U.S. Army recruited Lemkin to teach classes in military government, and the Board of Economic Warfare engaged him as a consultant.

In 1944, Lemkin published his most important work, Axis Rule in Occupied Europe, a legal analysis of Nazi-occupied Europe. In it he coined a new word, genocide, derived from the Greek word genos, meaning tribe, and the Latin word cide, meaning to kill.

Lemkin believed in the power of language—that part of what enabled civilized nations to commit intentional group destruction and the world to ignore these atrocities was the lack of a specific word to differentiate this sort of crime from others.  He viewed genocide as a unique crime because the ultimate goal of the perpetrator was the total destruction of an entire group of other human beings—the genocide not only of people, but also the destruction of their culture and civilizations.  

In Axis Rule in Occupied Europe, Lemkin noted that the harsh, racist decrees of the Nazis represented a perversion of the entire tradition of European jurisprudence. The Nazi edicts that, for instance, penalized the use of the Polish language or allotted food rations on the basis of "race" were both an expression of the intention to wipe out entire peoples and cultures and the framework that facilitated this annihilation.