Dubus grew up in the Bayou country in Lafayette, Louisiana, and was educated by the Christian Brothers, a Catholic religious order that emphasized literature and writing.

The family then moved to Haverhill, Massachusetts, where Dubus would spend the bulk of his academic career teaching literature and creative writing at Bradford College.

[5] Dubus carried personal firearms to protect himself and those around him, until the night in the late 1980s, when he almost shot a man who was in a drunken argument with his son, Andre, outside a bar in Haverhill, Massachusetts.

Despite his efforts to walk with a prosthesis, chronic infections led to him using a wheelchair for the remainder of his life, and he battled clinical depression as a result of his condition.

Dubus eventually continued to write after his accident and produced two books of essays—including Broken Vessels, which became a finalist for the Pulitzer Prize—and a collection of short stories.

Throughout his career, he published most of his work in small, distinguished literary journals such as Ploughshares[7] and Sewanee Review, though he also placed stories in magazines such as The New Yorker and Playboy.

When larger book publishers approached him with more lucrative deals, Dubus stayed with Godine, switching only to Alfred A. Knopf towards the end of his career to assist with medical bills.

Dubus's collections and novellas include: Separate Flights (1975), Adultery and Other Choices (1977), Finding a Girl in America (1980), The Times Are Never So Bad (1983), Voices from the Moon (1984), The Last Worthless Evening (1986), Selected Stories (1988), Broken Vessels (1991), Dancing After Hours (1996), and Meditations from a Movable Chair (1998).

Italian writer and editor Nicola Manuppelli has translated six collections of short stories and novellas by Dubus for Italian publisher Mattioli 1885: "Separate Flights" ("Voli separati"), "The Times Are Never So Bad" ("I tempi non sono mai così cattivi"), "Voices From The Moon" ("Voci dalla luna"), "We Don't Live Here Anymore" ("Non abitiamo più qui"), "Finding a girl in America" ("Il padre d'inverno") "Dancing After Hours" ("Ballando a notte fonda").

After Dubus's death, his story "Killings" was adapted into Todd Field's In the Bedroom (2001) starring Sissy Spacek, Tom Wilkinson, and Marisa Tomei.