He was a prolific and versatile writer publishing over three dozen books in several genres including poetry, fiction, nonfiction, children's literature, and memoir.

After a short stint as assistant professor of English at Stony Brook University (1965–66), Harrison started working full-time as a writer.

[9] His work has appeared in many leading publications, including The New Yorker, Esquire, Sports Illustrated, Rolling Stone, Outside, Playboy, Men's Journal, and The New York Times Book Review.

Many stories are set in places such as Nebraska's Sand Hills, Michigan's Upper Peninsula, Montana's mountains, and along the Arizona–Mexico border.

The actor Jack Nicholson, a close friend of Harrison's whom he had met through Thomas McGuane, played a peripheral role in the creation of that book.

[14] The title novella is an epic story that spans 50 years and tells the tale of a father and three sons in the vast spaces of the northern Rocky Mountains around the time of World War I.

Referring to the title novella, Harrison said:"I wrote Legends of the Fall in nine days and when I re-read it, I only had to change one word.

Following Legends of the Fall, seven more collections of novellas appeared over the course of Harrison's lifetime: The Woman Lit by Fireflies (1990), Julip (1994), The Beast God Forgot to Invent (2000), The Summer He Didn't Die (2005), The Farmer's Daughter (2009), The River Swimmer (2013), and finally The Ancient Minstrel (2016), the latter appearing just before Harrison's death in March of that year.

It is a complex tale, set in rural Nebraska, of a woman's search for the son she had given up for adoption and for the boy's father, who also happened to be her half-brother.

Throughout the narrative, Dalva invokes the memory of her pioneer great-grandfather John Wesley Northridge, an Andersonville survivor during the Civil War and naturalist, whose diaries vividly tell of the destruction of the Plains Indian way of life.

Many of these characters are featured also in The Road Home (1998), a complex work using five narrators, including Dalva, her 30-year-old son Nelse, and her grandfather John Wesley Northridge II.

After age 60, he published another dozen works of fiction, at least six more volumes of poetry, a memoir Off to the Side, and The Raw and the Cooked: Adventures of a Roving Gourmand, a collection of his food essays which had first appeared in magazines, mostly in Esquire and Men's Journal.

Although he continued writing in the novella format, during these final years (1999–2016), Harrison refocused his efforts on the longer novel form.

In the 2000s, Harrison published two of the most ambitious novels, setting them in Michigan's Upper Peninsula: True North (2004) and its sequel Returning to Earth (2007).

True North examines the costs to a timber and mining family torn apart by alcoholism and the moral recklessness of a war-damaged father.

Ultimately, the extended family helps Donald end his life at the place of his choosing, and then draw on the powers of love and commitment to reconcile loss and heal wounds borne for generations.

The Great Leader: A Faux Mystery was positively reviewed in The New York Times, with critic Pete Dexter calling Harrison's writing "very close to magic.

[22] He became aware of Zen inspired poetry "by way of poets like Clayton Eshleman and Cid Corman, and most powerfully of all through Gary Snyder"[23].

It was directed by Edward Zwick and starred Brad Pitt, Anthony Hopkins, and Aidan Quinn; it won the 1995 Academy Award for cinematography.

Other films he scripted or co-wrote include Cold Feet (1989), with Keith Carradine, Tom Waits, and Rip Torn, and Revenge (1990), starring Kevin Costner.

For his work on the screenplay for Wolf (1994, starring Jack Nicholson) Harrison, along with co-writer Wesley Strick, shared the Saturn Award for Best Writing.