Margulies was born in Brooklyn, New York City, New York, but was raised in Norwalk, Connecticut. After briefly attending Columbia University, Margulies began working for Munsey's Magazine, selling subsidiary rights to its stories. He later spent five years as head of East Coast research for Fox Films, a predecessor company of 20th Century Fox, and afterward became editorial chief of publisher Ned Pines' Standard Magazines. At one time in the 1930s, he reputedly edited 46 magazines, including the pulp magazines Startling Stories and Thrilling Wonder Stories.
After the war, Margulies helped launch Pines' Popular Library line of paperback books. He was co-editor of the anthology My Best Science Fiction Story in 1949 and went on to compile several science fiction and fantasy paperback anthologies. He was editor of Mike Shayne's Mystery Magazine at the time of his death.
Margulies was married to the former Cylvia Kleinman at the time of his death.
- "Leo Margulies; Long an Editor of Pulp Magazines, Dies at 75". The New York Times. December 29, 1975.
- Peter Nicholls (ed.), ed. (1979). Science Fiction Encyclopedia, The. London: Roxby Press Limited. ISBN 0-385-14743-0.
- Wooley, John and Locke, John. "A History of the Thrilling Pulps." Thrilling Detective Heroes [Adventure House, 2007].