Kowalski is the eldest child of Dr. William John Kowalski, Jr. of Buffalo, N.Y. (born 1942) and Kathleen Emily Siepel of Angola, N.Y. (b. 1942). In 1974, the family moved to Erie, Pennsylvania. He attended Erie Day School from 1976-1984, Cathedral Preparatory School for Boys from 1984-85, and McDowell High School from 1985-88, where he played bass in the rock group Gideon Winter and acted in numerous high school and community theater productions.

Kowalski has said that he realized he wanted to be a writer when he was about six years old, and that he began to pursue that dream soon after. In 1988, Kowalski attended the Mercyhurst College Summer Writer's Institute, where he studied under Dr. Ken Schiff (founder of the Institute) and the late W.S. "Jack" Kuniczak. He matriculated at Boston's Emerson College in 1988, where he majored in Creative Writing, but dropped out in 1989 to devote himself to writing full-time, believing that he was focusing too much on writing at the expense of gaining the life experiences he needed to have something to write about:

"We have far too many writers in America these days who are expert stylists but who really aren't writing about anything. They can write like hell, but they don't have much to say, because they haven't done anything except study writing. As soon as I realized I was in danger of having this happen to me, I dropped out of college.... Life makes writers--nothing else does."

As a result, he took a year off from school and worked at two now-defunct Boston bookstores, Avenue Victor Hugo and Globe Corner Bookstore.

In 1990, Kowalski matriculated at St. John's College in Santa Fe, New Mexico, a four-year program whose curriculum consists of the "Great Books" of Western Civilization, including not only literature, but also philosophy, mathematics, the sciences, music and art. He believes this program made him "more well-rounded, and as a result, a more interesting person...". While at St. John's, he was the first drummer for a swing group called The Swinging Recluses, which was fronted by the late singer Lhasa de Sela and led by the current Mayor of Annapolis, Joshua J. Cohen, who also played lead saxophone. Kowalski graduated in 1994 and entered the teaching profession, leaving it in 1998 after the sale of his first novel to HarperCollins Publishers.

Kowalski has stated that his literary influences include Ernest Hemingway and John Irving, Spanish-language authors Isabel Allende and Gabriel García Márquez, and more-populist authors like spy writer John le Carré, southwestern author Tony Hillerman and sea-story writer Patrick O'Brian.

Kowalski is the author of four works of literary fiction: Eddie’s Bastard (1999) and its sequel, Somewhere South of Here (2001); The Adventures of Flash Jackson (2003); and The Good Neighbor (2004), all published in the U.S. by HarperCollins and in the U.K. by Transworld/Doubleday/Black Swan. His books have appeared in translation and on bestseller lists around the world, including the Times of London.

In his New York Times review of Eddie’s Bastard, William J. Cobb complemented Kowalski for his style and exuberance but faulted him for making the novel both sentimental and anachronistic. But Los Angeles Times reviewer Mark Rozzo was more impressed, rejecting the charge of sentimentality and praising the work for its "enviably gentle pacing," "unflappable good nature" and "honeyed glow". The novel earned Kowalski a place in the Barnes & Noble Discover Great New Writers program in 1999 and won the 2001 Exclusive Books Boeke Prize (South Africa), putting his novel in the company of such other well-known novels as Midnight in the Garden of Good and Evil, The Poisonwood Bible, Life of Pi, The Kite Runner and The Girl with the Dragon Tattoo.

His sequel, Somewhere South of Here, was described by Elizabeth Judd as being confident and entertaining in the Kerouac mold, noting Kowalski's "talent for casual invention" and "bravado," even though it never reaches the "deeper truths" of its own story.

The Adventures of Flash Jackson was a Literary Guild Alternate Selection in 2003.

Kowalski's fifth novel, The Barrio Kings, will be published by Orca Publishers under their Raven imprint in April of 2010.

Kowalski is married to Alexandra Nedergaard (b. 1968) of Toronto, Ontario. They have two children and currently live in Nova Scotia, where he teaches at Nova Scotia Community College.