[3] The story begins with Detective Malone describing an on-duty incident in Red Hook, Brooklyn, that gave him a phobia of large buildings.

Back-tracking to where it all began, the Brooklyn waterfront slum Red Hook is described in detail, with its gangs and crime, and hinting at an occult underbelly.

The "case of Robert Suydam" is then told to be the driving force behind Malone's federally ordered involvement at Red Hook.

A police raid, involving Malone, uncovers nothing useful from Suydam's Red Hook flat save a few strange inscriptions.

The tunnels and chambers uncovered in the raids are filled in and cemented, though, as Malone recounts, the threat in Red Hook subtly re-emerges.

"The Horror at Red Hook" is not generally considered to be part of the Cthulhu Mythos, lacking many of the elements that characterize it, such as totally alien cults with cosmic purposes, forbidden tomes, unknown gods and a sense of true "outsideness", as the cult and occult magic in the story have decidedly real world origins and purposes.

The Martense Family were the subterranean cannibals in Lovecraft's earlier story "The Lurking Fear", who live in a location from which the river flows south to eventually emerge at Red Hook.

Beherec argues that the building's conversion from Suydam's Federalist tenement to a Gothic church by a sect he (erroneously) believed to be Nestorian, which began while he was in New York, inspired Lovecraft.

[9] Daniel Harms and John Wisdom Gonce note the spell Lovecraft quotes and describes as a "demon evocation", was actually an incantation allegedly used for treasure hunting.

Lovecraft himself, always modest about his work and at that time rather depressed, said of "The Horror at Red Hook" that the tale was "rather long and rambling, and I don't think it is very good".