He had success with several horror and supernatural fiction novels, among them Julia (1975), Ghost Story (1979) and The Talisman (1984), the latter co-written with Stephen King.

According to his New York Times obituary, Straub "brought a poet's sensibility to stories about ghosts, demons and other things that go bump in the night.

[6] Straub read voraciously from an early age, although his father hoped that he would grow up to be a professional athlete, and his mother wanted him to be a Lutheran minister.

[7] In high school, he "discovered Thomas Wolfe and Jack Kerouac, patron saints of wounded and self-conscious adolescence and also, blessedly, jazz music, which spoke in utterance of beyond any constraint: passion and liberation in the form of speech on the far side of the verbal border.

He briefly taught English at Milwaukee Country Day, where he "enjoyed a minor but temporary success as Mr. Chips-cum-jalapenos, largely due to the absolute freedom given him by the administration and his affection for his students, who faithfully followed him as he struck matches and led them into caves named Lawrence, Forster, Brontë, Thackeray, etc., etc.

"[9] After mixed success with two attempts at literary mainstream novels in the mid-1970s (Marriages and Under Venus), Straub dabbled in the supernatural for the first time with Julia (1975).

[10] He recalls that "The reason I chose to write scary books was because, at the time, there were three horror novels that had been enormously successful: The Exorcist, Rosemary's Baby and The Other.

"[11] He followed Julia with If You Could See Me Now (1977),[12] and came to widespread public attention with his fifth novel, Ghost Story (1979),[13] which was a critical success and was later loosely adapted into a 1981 film starring Fred Astaire.

[19] After a fallow period, Straub re-emerged in 1988 with Koko, a non-supernatural (though horrific) novel about the Vietnam war.

The three novels comprise the "Blue Rose Trilogy", which extended Straub's experiments with metafiction and unreliable narrators.

[21][22] In 1990, Straub published Houses Without Doors, a collection of short fiction including the shorter version of the novella Mrs. God.

[29] My Life in Pictures appeared in 1971 as part of a series of six poetry pamphlets Straub published with his friend Thomas Tessier under the Seafront Press imprint while living in Dublin.

[29][31] Straub's third book of poetry, Open Air, appeared later that same year from Irish University Press.

A critical essay on Straub's horror work can be found in S. T. Joshi's book The Modern Weird Tale (2001).

[43] In Andrew Shaffer's Secret Santa, a character refers to Stephen King, Anne Rice and Straub as "the unholy trinity" of horror.

"[48] Straub was a jazz aficionado, and saxophonist Lester Young features in his novella Pork Pie Hat.

He gravitated toward Dave Brubeck & Paul Desmond, Clifford Brown, Bill Evans and Miles Davis.