Les Bienveillantes (The Well-Meaning Ones) had attracted widespread attention in France for its treatment of a controversial subject even before it won the award on Monday.
The American author burst onto the French literary scene barely two-and-a-half months ago, having chosen to write his debut novel in French.
"It's certainly linked to my literary tradition which is more French than Anglo-Saxon," Littell said.
He first drafted Les Bienveillantes over four months while living in Moscow.
The book, which has topped French bestseller lists for weeks, will be published in the United States in 2008, following an extensive bidding war won by HarperCollins.
Born in New York to a Jewish family of Polish origin, the 39-year-old grew up in France where he lived until the age of 18, before returning to the United States to attend university.
"For me, the essential thing is the question of the torturer, of political murder, of state murder"
Jonathan Littell, American author
Littell had worked for eight years for the French charity Action Contre La Faim [Action Against Hunger] in Bosnia, Rwanda, Chechnya and Afghanistan.
He decided in January 2001 to "stop everything" and write instead.
His experience in the field only fed into the tale of barbarism and the bureaucracy of horror, he said.
"For me, the essential thing is the question of the torturer, of political murder, of state murder," Littell said.
"What interested me was to understand what led people to become torturers."
Peter Shoettler, Franco-German historian, called the book a "strange, monstrous book", explicit to the point of "pornography" on the horrors of the Holocaust.
But Littell, a discreet man by nature who has largely shied away from publicity since his book was published, has refused to enter into the public debate on how his novel may be received.
"Once I've finished the book, the line is drawn. It's an object on the table, people can do what they want," he said.