Dorothy B. Hughes was born in Kansas City, Missouri. She knew from the age of six, when she learned to write words, that she would be a writer. She studied journalism at the University of Missouri, did graduate work at the University of New Mexico and also attended Columbia University in New York. Before starting her career as a mystery writer, Hughes worked as a journalist in Missouri, New York and New Mexico.
Hughes wrote fourteen crime and mystery novels. Her best-known works include Ride the Pink Horse (1946) and In a Lonely Place (1947), perhaps her greatest novel, which was filmed with Humphrey Bogart in 1950.
At the peak of her career Hughes stopped writing novels, explaining that her domestic responsibilities made writing difficult: her mother was ill, she was taking care of her grandchildren and she simply hadn't the tranquility required to write.
From 1940 to 1979 she reviewed mysteries for the Albuquerque Tribune, Los Angeles Times, New York Herald-Tribune and other newspapers. In 1978 Hughes was named a Grand Master by the Mystery Writers of America. She won her second Edgar Allan Poe award for her critical biography Erle Stanley Gardner: The CaseE of Real Perry Mason.
Most of Hughes's detective fiction centres around outsiders, haunted loners, or upper-class characters involved in evil intrigues. Hughes herself acknowledged her debt to such writers as Eric Ambler, Graham Greene and William Faulkner.
Hughes lived and worked for the majority of her life in New Mexico. She died on 6 May 1993.