His best-known characters are the detective Nero Wolfe and his assistant Archie Goodwin, who were featured in 33 novels and 39 novellas or short stories between 1934 and 1975.

Stout was active in the early years of the American Civil Liberties Union and a founder of the Vanguard Press.

Ironically, just as Stout was starting to write fiction again, he lost most of the money that he had made as a businessman in the Great Depression of 1929.

In the 1930s, Stout turned to writing detective fiction, a genre that he and Farrar thought might be more financially rewarding than his previous novels.

The novel was published by Farrar & Rinehart in October 1934, and in abridged form as "Point of Death" in The American Magazine (November 1934).

Beginning in 1940, Nero Wolfe began to appear in novellas as well as full-length novels, at the behest of his editors at The American Magazine.

During World War II, Stout cut back on his detective writing to focus on war-related activities.

After the war, in addition to continuing to write the Nero Wolfe books, Stout supported democracy and world government.

Stout was a longtime friend of British humorist P. G. Wodehouse, writer of the Jeeves novels and short stories.

During his tenure, Vanguard issued 150 titles, including seven books by Scott Nearing and three of Stout's own novels—How Like a God (1929), Seed on the Wind (1930), and Golden Remedy (1931).

He developed an extreme anti-German attitude and wrote the provocative essay "We Shall Hate, or We Shall Fail"[8] which generated a flood of protests after its January 1943 publication in The New York Times.

"Hundreds of Axis propaganda broadcasts, beamed not merely to the Allied countries but to neutrals, were sifted weekly", wrote Stout's biographer John McAleer.

"Rex himself, for an average of twenty hours a week, pored over the typewritten yellow sheets of accumulated data ... Then, using a dialogue format – Axis commentators making their assertions, and Rex Stout, the lie detective, offering his refutations – he dictated to his secretary the script of the fifteen-minute broadcast."

By November 1942, Berlin Radio was reporting that "Rex Stout himself has cut his own production in detective stories from four to one a year and is devoting the entire balance of his time to writing official war propaganda."

"[1]: 121–122 [2]: 305–307 In September 1942, Stout defended FDR's policy of sending Japanese-Americans to concentration camps in a debate with the Socialist civil libertarian Norman Thomas.

[12]: 216–217, 227 [d][e] In later years, Stout alienated some readers[specify] with his hawkish stance on the Vietnam War and with the contempt for communism expressed in certain of his works.

The latter viewpoint is given voice in the 1952 novella "Home to Roost" (first published as "Nero Wolfe and the Communist Killer") and most notably in the 1949 novel The Second Confession.

[14] If he had done nothing more than to create Archie Goodwin, Rex Stout would deserve the gratitude of whatever assessors watch over the prosperity of American literature.

[2]: 578 [g][h] "He read Hegel, Heidegger and Sartre, as well as Dashiell Hammett, Rex Stout and Georges Simenon," the Times Higher Education Supplement wrote of Magritte.

"[20] Magritte's 1942 painting Les compagnons de la peur ("The Companions of Fear") bears the title given to The League of Frightened Men (1935) when it was published in France by Gallimard (1939).

[citation needed] The archival papers of Rex Stout anchor Boston College's collection of American detective fiction.