Hoch (pronounced hoke) was born in Rochester, New York and began writing in the 1950s; his first story appeared in 1955 in Famous Detective Stories and was followed by stories in The Saint Mystery Magazine. In January 1962 he began appearing in Alfred Hitchcock's Mystery Magazine. In December 1962 he kicked off his most successful collaboration, with the appearance of his first story in Ellery Queen's Mystery Magazine; in the years since EQMM has published over 450 of Hoch's stories, roughly half of his total output. In May 1973 EQMM began publishing a new Hoch story in every monthly issue; as of May 2007 the author had gone an astonishing 34 years without missing a single issue.

Hoch was a master of the classic detective story, emphasizing mystery and deduction rather than suspense and fast action; EQMM has called him "The King of the Classical Whodunit." His stories are very well written and are usually tightly plotted puzzles, with carefully and fairly presented clues, both physical and psychological. He was particularly partial to "impossible crime" tales, where to all appearances the crime (usually a murder) could not have been committed at all; he invented numerous variants on the locked room mystery popularized by John Dickson Carr and others. For instance, in "The Second Problem of the Covered Bridge", a man is shot at close range while alone on a covered bridge, while crowds of witnesses watch both ends of the bridge.

Hoch also published magazine stories under the names "Stephen Dentinger", "R. L. Stevens", "Pat McMahon", "Anthony Circus", "Irwin Booth", "R. E. Porter", "Mr. X" and the House Name "Ellery Queen". In many cases he also had a story under his own name in the same magazine issue. Hoch also wrote a novel published as Ellery Queen, under the supervision and editing of Manfred Lee, half of the writing partnership known as Ellery Queen.

In 2001 Hoch was named a Grand Master by the Mystery Writers of America, the first time a Grand Master was known primarily for short fiction rather than novels.

Edward D. Hoch died at home in Rochester of a heart attack. His wife, née Patricia McMahon, was his only immediate survivor. Hoch was 77 at his death.

The overwhelming majority of Hoch's stories feature series characters. He has created at least a dozen different series of stories for EQMM alone. His Captain Leopold series reached over 100 stories.

These three science fiction novels, set in the mid-21st century, feature Carl Crader and Earl Jazine of the Computer Investigation Bureau, nicknamed the "Computer Cops".