He gave first directing opportunities to Robert Wise and Mark Robson and worked with Boris Karloff, who credited Lewton with saving his career.

In 1909, they emigrated to the United States as second cabin class passengers on board the SS Amerika, which sailed from Hamburg, 29 April, and arrived in New York, 8 May; they were listed as Anna, Olga and Volodymyr Hofschneider.

In 1920, when Lewton was 16, he lost his job as a society reporter for the Darien-Stamford Review after it was discovered that a story he wrote about a truckload of kosher chickens dying in a New York heat wave was a total fabrication.

[5] Lewton worked as a writer at MGM's publicity office in New York City, providing novelizations of popular movies for serialization in magazines, which were sometimes later collected into book form.

He quit this position after the success of No Bed of Her Own, but when three later novels that same year failed to succeed, he journeyed to Hollywood for a job writing a screen treatment of Gogol's Taras Bulba for David O. Selznick.

Lewton also worked as an uncredited writer for Selznick's Gone with the Wind, including writing the scene where the camera pulls back to reveal hundreds of wounded soldiers at the Atlanta depot.

Lewton always wrote the final draft of the screenplays for his films, but avoided on-screen co-writing credits except in two cases, The Body Snatcher and Bedlam, for which he used the pseudonym "Carlos Keith," which he had previously used for the novels 4 Wives, A Laughing Woman, This Fool, Passion, and Where the Cobra Sings.

After RKO promoted Tourneur to A-films, Lewton gave first directing opportunities to Robert Wise and Mark Robson.

Berg wrote, "Mr. Karloff has great love and respect for Mr. Lewton as the man who rescued him from the living dead and restored, so to speak, his soul.

Lewton spent time at home working on a screenplay about the famous American Revolutionary War battles at Fort Ticonderoga.

Universal Studios made an offer on the work, and though the screenplay was not used, Lewton was given producer duties on the film Apache Drums, released in 1951.

Lewton resigned at Universal and began preparation to work on the film My Six Convicts, but after suffering gallstone problems, he had the first of two heart attacks which weakened him so much that he died at Cedars-Sinai Medical Center in 1951 at the age of 46.

In May 2017, The Secret History Of Hollywood, a podcast biopic series by Adam Roche, began an eleven-part season on his life and work – “Shadows” – featuring Mark Gatiss.