Gorey has become an iconic figure in the goth subculture. Events themed on his works and decorated in his characteristic style are Common in the more Victorian-styled elements of the subculture, notably the Edwardian costume balls held annually in San Francisco and Los Angeles, which include performances based on his works. The "Edwardian" in this case refers less to the Edwardian period of history than to Gorey, whose characters are depicted as wearing fashion styles ranging from those of the mid-nineteenth century to the 1930s.

Edward St. John Gorey was born in Chicago. His parents, Helen Dunham (née Garvey) and Edward Lee Gorey, divorced in 1936 when he was 11, then remarried in 1952 when he was 27. One of his stepmothers was Corinna Mura (1909–1965), a cabaret singer who had a small role in the classic film Casablanca as the woman playing the guitar while singing "La Marseillaise" at Rick's Café Américain. His Father was briefly a Journalist. Gorey's maternal great-grandmother, Helen St. John Garvey, was a popular nineteenth-century greeting card Writer and Artist, from whom he claimed to have inherited his talents.

He frequently stated that his formal art training was "negligible"; Gorey studied art for one semester at the School of the Art Institute of Chicago in 1943.

Gorey attended a variety of local grade schools and then the Francis W. Parker School. He spent 1944 to 1946 in the Army at Dugway Proving Ground in Utah. He then attended Harvard University, beginning in 1946 and graduating in the class of 1950; he studied French and roomed with poet Frank O'Hara.

In the early 1950s, Gorey, with a group of recent Harvard alumni including Alison Lurie (1947), John Ashbery (1949), Donald Hall (1951) and Frank O'Hara, amongst others, founded the Poets' Theatre in Cambridge, which was supported by Harvard faculty members John Ciardi and Thornton Wilder.

His first independent work, The Unstrung Harp, was published in 1953. He also published under various pen names, some of which were anagrams of his first and last names, such as Ogdred Weary, Dogear Wryde, Ms. Regera Dowdy, and dozens more. His books also feature the names Eduard Blutig ("Edward Gory"), a German language pun on his own name, and O. Müde (German for O. Weary).

In 1976, jazz Composer Michael Mantler recorded an album called The Hapless Child (Watt/ECM) with Robert Wyatt, Terje Rypdal, Carla Bley, and Jack DeJohnette. It contains musical adaptations of The Sinking Spell, The Object Lesson, The Insect God, The Doubtful Guest, The Remembered Visit, and The Hapless Child. The last three songs also have been published on his 1987 Live album with Jack Bruce, Rick Fenn, and Nick Mason.

Gorey's illustrated (and sometimes wordless) books, with their vaguely ominous air and ostensibly Victorian and Edwardian settings, have long had a cult following. He made a notable impact of the world of theater with his designs for the 1977 Broadway revival of Dracula, for which he won the Tony Award for Best Costume Design and was nominated for the Tony Award for Best Scenic Design. In 1980, Gorey became particularly well known for his animated introduction to the PBS series Mystery! In the introduction of each Mystery! episode, host Vincent Price would welcome viewers to "Gorey Mansion".

Because of the settings and style of Gorey's work, many people have assumed he was British; in fact, he only left the U.S. once, for a visit to the Scottish Hebrides. In later years, he lived year-round in Yarmouth Port, Massachusetts, on Cape Cod, where he wrote and directed numerous evening-length entertainments, often featuring his own papier-mâché puppets, an ensemble known as Le Theatricule Stoique. The first of these productions, Lost Shoelaces, premiered in Woods Hole, Massachusetts on August 13, 1987. The last was The White Canoe: an Opera Seria for Hand Puppets, for which Gorey wrote the libretto, with a score by the Composer Daniel James Wolf. Based on Thomas Moore's poem The Lake of the Dismal Swamp, the opera was staged after Gorey's death and directed by his friend, neighbor, and longtime collaborator Carol Verburg, with a puppet stage made by his friends and neighbors, the noted set designers Herbert Senn and Helen Pond. In the early 1970s, Gorey wrote an unproduced screenplay for a silent film, The Black Doll.

From 1995 to his death in April 2000, the normally reclusive Artist was the subject of a cinéma vérité-style documentary directed by Christopher Seufert. (As of 2016, the film has been screened as a work-in-progress; the finished film and accompanying book are slated for 2017.) He was interviewed on Tribute to Edward Gorey, an hour-long community, public-access television cable show produced by Artist and friend Joyce Kenney. He contributed his videos and personal thoughts. Gorey served as a judge at Yarmouth art shows and enjoyed activities at the local cable station, studying computer art and serving as cameraman on many Yarmouth shows. His Cape Cod house is called Elephant House and is the subject of a photography book entitled Elephant House: Or, the Home of Edward Gorey, with photographs and text by Kevin McDermott. The house is now the Edward Gorey House Museum.

Director Mark Romanek's music video for the Nine Inch Nails song "The Perfect Drug" was designed specifically to resemble a Gorey book, with familiar Gorey elements including oversized urns, topiary plants and glum, pale characters in full Edwardian costume. Also, Caitlín R. Kiernan has published a short story entitled "A Story for Edward Gorey" (Tales of Pain and Wonder, 2000), which features Gorey's black doll.

A more direct link to Gorey's influence on the music world is evident in The Gorey End, an album recorded in 2003 by The Tiger Lillies and the Kronos Quartet. This album was a collaboration with Gorey, who liked previous work by The Tiger Lillies so much that he sent them a large box of his unpublished works, which were then adapted and turned into songs. Gorey died before hearing the finished album.

In 2007, The Jim Henson Company announced plans to produce a feature film based on The Doubtful Guest to be directed by Brad Peyton. No release date was given and there has been no further information since the announcement.

The online journal Goreyesque publishes artwork, stories, and poems in the spirit of Edward Gorey's work. The journal is co-sponsored by the Department of Creative Writing at Columbia College Chicago and Loyola University Chicago. Goreyesque was launched in tandem with the Chicago debut of two Gorey collections: Elegant Enigmas: The Art of Edward Gorey and G is for Gorey. The collections were shown at the Loyola University Museum of Art (LUMA) in Chicago, Illinois from February 15 to June 15, 2014. Goreyesque features the work of both emerging talents and seasoned professionals, such as Writers Sam Weller and Joe Meno.