Helen McCloy was born in New York City. Her mother was the writer Helen Worrell McCloy and father, William McCloy, was the longtime managing editor of the New York Evening Sun. She was educated at the Friend's School, run by Brooklyn's Quaker community. In 1923 she went to France and studied at the Sorbonne. After finishing her studies, she worked for Hearst's Universal News Service (1927 - 1932). Then she was an art critic for International Studio and other magazines, and free-lance contributor to London Morning Post and Parnassus. She returned to the United States in 1932.

In 1946 McCloy married Davis Dresser, who had gained fame with his Mike Shayne novels, written under the pseudonym Brett Halliday. She founded with Dressler the Torquil Publishing Company and a literary agency (Halliday and McCloy). Their marriage ended in 1961. In the 1950s and 1960s McCloy was a co-author of review column for Connecticut newspapers and in 1950 she became the first woman to serve as president of Mystery Writers of America. In 1954 she received Edgar from the same organization for her critics. McCloy helped to found in 1971 a New England chapter of the Mystery Writers of America in Boston.

Having read Sherlock Holmes as a young girl, McCloy retained an interest in mysteries and began to write them in the 1930s. Her first novel, Dance of Death, was published in 1938. It was followed by several other mystery publications in the 1940s. Cue for Murder (1942) was a story of murder onstage during a Broadway revival of Sardou's Fédora. The One That Got Away (1945) explored the psychology of Fascism, postulating that it is rooted in woman hatred, and rejection of a mother's tender care of children. A non-Willing mystery, Panic (1944), was set in a remote cottage in the Catskills and was notable for its use of cryptoanalysis.

In Mr. Splitfoot (1968) Dr. Willing and his wife to take shelter at a remote house in New England, where they must lodge in a haunted room. The title refers to the Devil, but Mr Splitfoot is also a symbol for the two sides of our nature, as Willing points out. The critic and mystery writer H.R.F. Keating included the work in 1987 among the 100 best crime and mystery books ever published.

Another masterpiece is the eighth Basil Willing novel, Through a Glass, Darkly (1950), a supernatural puzzle in the tradition of John Dickson Carr. "If you want to scare yourself still in bed, it's just the thing for you," the English writer Pamela Hansford Johnson said of the book.

In The Impostor (1977) a woman, Marina, recovers consciousness after a car crash to find herself in a psychiatric clinic. She recalls the accident clearly but she's told that all is her delusion. A man arrives, not her husband, but the get away she accepts the impostor. McCloy used in the story a cryptological double bluff. She had read about it in 1944 when she was writing Panic, but because she was unable to trace the source, she improvised her own version of it.

Series of Dr. Basil Willing

• Dance of Death (1938)
• The Man in the Moonlight (1940)
• The Deadly Truth (1941)
• Who's Calling (1942)
• Cue for Murder (1942)
• The Goblin Market (1943)
• The One That Got Away (1945)
• Through a Glass, Darkly (1950)
• Alias Basil Willing (1951)
• The Long Body (1955)
• Two-Thirds of a Ghost (1956)
• Mr. Splitfoot (1968)
• Burn This (1980)
• The Pleasant Assassin and Other Cases of Dr. Basil Willing (Short Stories) (2003)

Non-series

• Do Not Disturb (1943)
• Panic (1944)
• She Walks Alone (1948)
• Better Off Dead (1951)
• Unfinished Crime (1954)
• The Slayer and the Slain (1957)
• Before I Die (1963)
• The Singing Diamonds and Other Stories (Short Stories) (1965)
• The Further Side of Fear (1967)
• A Question of Time (1971)
• A Change of Heart (1973)
• The Sleepwalker (1974)
• Minotaur Country (1975)
• The Changeling Conspiracy uk title: Cruel as the grave(1976)
• The Impostor (1977)
• The Smoking Mirror (1979)

Written as Helen Clarkson

• The Last Day (1959)