Lucille Fletcher was born in Brooklyn, New York, and began writing as a child. She attended Bay Ridge High School and was editor of the school magazine. In 1929, at age 17, she placed third in the National Oratorical Contest on the Constitution of the United States, judged by five justices of the Supreme Court. She graduated with honors from Vassar College in 1933, and went to work as a typist, music librarian, and publicity writer at CBS. There she met her future husband, Bernard Herrmann, composer and conductor of the CBS orchestra; they married in 1939 and had two daughters. In 1940, she began her radio career when a magazine story she had written, "My Client Curley," was made into a radio play; it was later adapted for the 1944 film Once Upon a Time. Her famous radio script "Hitchhiker" was first performed by Orson Welles on his radio program.
"Sorry, Wrong Number," which premiered in 1943 as an episode of the radio series Suspense, transfixed audiences; it was broadcast nationwide seven times between 1943 and 1948, and was adapted for a 1948 film. It also won an Edgar from the Mystery Writers of America, inspired two operas, and became a television drama in 1989. In the late 1950s, she began writing novels, which included Blindfold (1960), adapted into a 1966 film; And Presumed Dead (1963); The Girl in Cabin B54 (1968) and Eighty Dollars to Stamford (1975).
In 1972, her suspense play ''Night Watch,'' was produced on Broadway and became a film the following year.