Smith worked as a journalist for sixteen years, beginning as a reporter for the New Orleans Times-Picayune. She then moved on to the San Francisco Chronicle, where she eventually became the first woman hired for the newsroom since World War II and spent the next ten years as a general assignment and court reporter. She later worked for the Santa Barbara News-Press, for Banana Republic as an advertising and catalogue copy writer, and for the San Francisco District Attorney's office as a public information officer.

She quit the Chronicle in 1979 to form a freelance writing and editing firm called Invisible Ink with several other aspiring fiction writers, including Marcia Muller. In 1982 Smith published her first novel.

In 1991, she became the first American woman since 1956 to win the Edgar for Best Novel. Her latest novel is P.I. On A Hot Tin Roof (2005), and New Orleans Noir, an anthology she edited, was published in 2007.

She currently lives in the Faubourg Marigny section of New Orleans.

In 2006 she founded Writerstrack.com, a course of writing instruction done through conference calls.

Novels

• Death Turns A Trick (Walker & Co., 1982)
• The Sourdough Wars (Walker & Co., 1984)
• True-Life Adventure (Mysterious Press, 1985)
• Tourist Trap (Mysterious Press, 1986)
• Huckleberry Fiend (Mysterious Press, 1987)
• New Orleans Mourning (St. Martin's Press, 1990)
• The Axeman's Jazz (St. Martin's Press, 1991)
• Dead in the Water (Ivy, 1991)
• Other People's Skeletons (Ivy, 1993)
• Jazz Funeral (Fawcett/Columbine, 1993)
• New Orleans Beat (Fawcett/Columbine, 1994)
• House of Blues (Fawcett/Columbine, 1995)
• The Kindness of Strangers (Fawcett/Columbine, 1996)
• Crescent City Kill (Fawcett/Columbine, 1997)
• 82 Desire (Fawcett/Columbine, 1998)
• Louisiana Hotshot (Forge, 2001)
• Louisiana Bigshot (Forge, 2002)
• Mean Woman Blues (Forge, 2003)
• Louisiana Lament (Forge, 2004)
• P.I. On A Hot Tin Roof (Forge, 2005)

Short stories

• "Grief Counselor", Mike Shayne Mystery Magazine, 1978; reprinted in Miniature Mysteries: 100 Malicious Little Mystery Stories, edited by Isaac Asimov, Martin H. Greenberg, and Joseph D. Olander (Taplinger, 1981), and in Last Laughs: The 1986 Mystery Writers of America Anthology, edited by Gregory McDonald (Mysterious Press, 1986)
• "The Wrong Number", Mike Shayne Mystery Magazine, 1979
• "Crime Wave in Pinhole", Alfred Hitchcock's Mystery Magazine, 1980; reprinted in The Arbor House Treasury of Mystery and Suspense, edited by Bill Pronzini, Barry N. Malzberg, and Martin H. Greenberg (Arbor House, 1981)
• "Project Mushroom", Ellery Queen's Mystery Magazine 1983; reprinted in 101 Mystery Stories, edited by Bill Pronzini and Martin H. Greenbery (Avenel, 1986)
• "Red Rock", Raymond Chandler's Philip Marlowe: A Centennial Celebration, edited by Byron Preiss (Knopf, 1988)
• "Blood Types", Sisters In Crime, edited by Marilyn Wallace (Berkley, 1989)
• "Cul-de-Sac", Sisters In Crime II, edited by Marilyn Wallace (Berkley, 1990)
• "Montezuma's Other Revenge", Justice for Hire, edited by Robert J Randisi (Mysterious Press, 1990)
• "A Marriage Made in Hell", Eye of a Woman, edited by Sara Paretsky (Delacorte Press, 1991)
• "Silk Strands", Deadly Allies, edited by Marilyn Wallace and Robert J. Randisi (Bantam, 1992)
• "Strangers on a Plane", Unusual Suspects, edited by James Grady, (Black Lizard Press, 1996)
• "The End of the Earth", Detective Duos, edited by Marcia Muller and Bill Pronzini (Oxford University Press, 1997)
• "Where The Boys Are", Mary Higgins Clark Mystery Magazine, September 1998
• "Too Mean to Die", Blue Lightning, edited by John Harvey (Slow Dancer Press, 1998)
• "Fresh Paint", Irreconcilable Differences, edited by Lia Matera (HarperCollins, 1999)
• "Always Othello", Mary Higgins Clark Mystery Magazine, June 1999
• "Let's Go Knock Over Seaside", Murder and Magnolias (HarperCollins 2000)
• "Kid Trombone", Murder And All That Jazz (Signet, 2004)

Essay

• "Splendor in the Mildew", A Place Called Home, edited by Mickey Perlman (St. Martin's Press, 1996)

Progressive novel

• I'd Kill For That, edited by Marcia Talley (St. Martin's, 2004) (With twelve other writers, including Rita Mae Brown, Linda Fairstein, Kathy Reichs, Jennifer Crusie, Anne Perry, and Katherine Neville)

Edited

• New Orleans Noir (Akashic, 2007)