Harrison was born in Grayling, Michigan, to Winfield Sprague Harrison, a county agricultural agent, and Norma Olivia (Wahlgren) Harrison, both avid readers.

He has been blind in one eye since childhood ("My left eye is blind and jogs like/a milky sparrow in its socket.") When he was 21 his father and sister died in an automobile accident. He was educated at Michigan State University where he received his B.A. (1960) and M.A. (1964) in comparative literature. He married Linda King in 1959 with whom he has two daughters. After a short stint as assistant professor of English at State University of New York, Stony Brook (1965—66), he became a full-time writer. His awards include National Academy of Arts grants (1967, 68, 69), a Guggenheim Fellowship (1969—70), the Spirit of the West Award from the Mountain & Plains Booksellers Association, and election to the American Academy of Arts and Letters (2007).

His work has appeared in many leading publications: The New Yorker, Esquire, Sports Illustrated, Rolling Stone, Outside, Playboy, Men's Journal, and The New York Times Book Review. He has published several collections of novellas, two of which were eventually turned into films: Revenge (1990) and Legends of the Fall (1994).

Much of Harrison's writing depicts sparsely populated regions of North America with many stories set in places such as Nebraska's Sand Hills, Michigan's Upper Peninsula, Montana's mountains, and along the Arizona-Mexico border.

He currently divides his residence, living in both Patagonia, Arizona and Livingston, Montana. On August 31, 2009, Harrison was featured in an episode of Anthony Bourdain's television show "No Reservations" that took place in and around Livingston.

Though famous for fiction, Harrison considers himself, first and foremost, a poet. In the Introduction to The Shape of the Journey (Copper Canyon Press, 1998), a collection drawn from his first eight books of poetry, he writes: "This book is the portion of my life that means the most to me....in poetry our motives are utterly similar to those who made cave paintings or petroglyphs, so that studying your own work of the past is to ruminate over artifacts, each one a signal, a remnant of a knot of perceptions that brings back to life who and what you were at that time, the past texture of what has to be termed as your ‘soul life.’" Poetry suffuses everything Harrison writes. "It’s totally uncontrollable," he says. "You don’t have any idea when its going to emerge, and when it’s not going to emerge. I’ve never stopped writing it....You can put off a novel for a while but you can’t not write a poem because that particular muse is not very cooperative." Harrison’s poetry has drawn from traditions as diverse as the Russian modernist Sergei Yesenin (Letters to Yesenin, 1973), Zen literary traditions (After Ikkyu and Other Poems, 1996), and the American-English traditions of nature-writing (Saving Daylight, 2006) leading back through Wordsworth. Whether writing short lyrics (Returning to Earth, 1977) or expansive suites (Locations, 1968), he has proven to be a master of form and perception. His most recent collection of poetry is In Search of Small Gods (Copper Canyon Press, 2009). In it he writes of the natural world he knows well. Many of his small gods are dogs, fish and birds, and he looks at them with awe and ironic amusement. Harrison discusses his poetry in an extensive interview in Five Points Magazine.

The impetus for novel-writing followed an accident in which Harrison fell off a cliff while bird hunting. During the ensuing recovery, his friend Thomas McGuane suggested he write a novel. Wolf; A False Memoir (1971) was the result. It is the story of a man who tells his life story while searching for signs of a wolf in the northern Michigan wilderness. This was followed by A Good Day to Die (1973), an ecotage novel and statement about the decline of American ecological systems, and Farmer (1976), a Lolita-like account of a country school teacher and farmer coming to grips with middle age, his mother’s dying, and complications of human sexuality.

Harrison’s first novellas were published in 1979 under the title Legends of the Fall. The title novella is an epic story that spans fifty 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. Film rights for all three stories in the book were sold, and Harrison eventually transformed himself into a screen-writer. Films he has scripted or co-written include Cold Feet (1989) with Keith Carradine, Tom Waits and Rip Torn; Revenge (1990) starring Kevin Costner; and Wolf (1994) starring Jack Nicholson. All the while he has continued to publish fiction and poetry. Four more collections of novellas (The Woman Lit by Fireflies (1990), Julip (1994), The Beast God Forgot to Invent (2000) and The Summer He Didn’t Die (2005)) followed.

After publishing Warlock (1981) and Sundog (1984), Harrison published what is perhaps his most famous novel Dalva (1988). 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 and naturalist whose diaries vividly tell of the destruction of the Plains Indian way of life. Many of these characters once again appear 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. What Harrison was trying to get at in this sequel to Dalva was "the soul history of where you live," in this case rural Nebraska in the latter half of the 20th century.

Harrison’s next two novels are set in Michigan’s remote Upper Peninsula. True North (2004) examines the paralyzing cost to a timber and mining family torn apart by alcoholism and moral recklessness of a war-damaged father. The novel contains two stories: that of the monstrous father and the son’s trying to atone for his father’s evil and, ultimately, reconciling with his family’s history. Returning to Earth (2007) revisits the setting and characters of True North (2004) some thirty years later. The story has four narrators: Donald, a mixed-blood Indian, now middle-aged and dying of Lou Gehrig’s disease; Donald’s wife, Cynthia, whom he rescued as a teen from the ruins of her family; Cynthia’s brother David (the central character of True North); and her nephew and Donald’s soul mate K. 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. Harrison’s most recent novel, The English Major (2008) is a road novel about a sixty year old former high school English teacher and farmer from Michigan who, after a divorce and the sale of his farm, heads westward on a mind-clearing road trip. Along the way he falls into an affair with a former student, reconnects with his big-shot son in San Francisco, confers on questions of life and lust with an old doctor friend, and undertakes his magnum opus of renaming all the states and their state-birds.

In June 2009, University of Nebraska Press will publish an extensive and up-to-date illustrated guide to Harrison’s published works. This work (edited by Gregg Orr and Beef Torrey) contains more than 1600 citations of writing by and about Harrison. Many of Harrison’s papers are housed at Grand Valley State University in Grand Rapids, Michigan.

Fiction

• Wolf: A False Memoir (1971)
• A Good Day to Die (1973)
• Farmer (1976)
• Legends of the Fall (Three novellas: "Revenge" "The Man Who Gave Up His Name" "Legends of the Fall") (1979)
• Warlock (1981)
• Sundog: The Story of an American Foreman, Robert Corvus Strang (1984)
• Dalva (1988)
• The Woman Lit By Fireflies (Three novellas: "Brown Dog" "Sunset Limited" "The Woman Lit by Fireflies") (1990)
• Julip (Three novellas: "Julip" "The Seven-Ounce Man" "The Beige Dolorosa") (1994)
• The Road Home (1998)
• The Beast God Forgot to Invent (Three novellas: "The Beast God Forgot to Invent" "Westward Ho" "I Forgot to Go to Spain") (2000)
• True North (2004)
• The Summer He Didn't Die (Three novellas: "The Summer He Didn't Die" "Republican Wives" "Tracking") (2005)
• Returning To Earth (Grove Press - January 2007)
• The English Major (2008)
• The Farmer's Daughter (2009)

Nonfiction

• Just Before Dark: Collected Nonfiction (1991)
• The Raw and the Cooked (1992) Dim Gray Bar Press ltd ed
• The Raw and the Cooked: Adventures of a Roving Gourmand (2001)
• Off to the Side: A Memoir (2002)

Children's literature

• The Boy Who Ran to the Woods (Illustrated by Tom Pohrt) (2000)

Poetry

• Plain Song (1965)
• Walking (1967)
• Locations (1968)
• Outlyer and Ghazals (1971)
• Letters to Yesenin (1973)
• Returning to Earth (Court Street Chapbook Series) (1977)
• Selected and New Poems, 1961-1981 (Drawings by Russell Chatham) (1981)
• Natural World: A Bestiary (1982)
• The Theory & Practice of Rivers (1986)
• The Theory & Practice of Rivers and New Poems (1989)
• After Ikkyu and Other Poems (1996)
• The Shape of the Journey: New and Collected Poems (Copper Canyon Press, 1998)
• Braided Creek: A Conversation in Poetry (with Ted Kooser) (Copper Canyon Press, 2003)
• Livingston Suite (Illustrated by Greg Keeler) (2005)
• Saving Daylight (Copper Canyon Press, 2006)
• In Search of Small Gods (Copper Canyon Press, 2009)