Barker was born to a working class family in Thornaby-on-Tees in the North Riding of Yorkshire, England, on 8 May 1943. Her mother Moyra died in 2000, and her father's identity is unknown. According to the British newspaper The Times, Moyra became pregnant “after a drunken night out while in the Wrens,” and later told people that Barker was her sister, rather than her daughter. They lived with Barker's grandmother Alice and step-grandfather William, until her mother married and moved out when Barker was seven. Barker could have joined her mother, she told the Guardian in 2003, but chose to stay with her grandmother "because of love of her, and because my stepfather didn't warm to me, nor me to him". Her grandparents ran a Fish and chip shop which failed and the family was, she told the Times in 2007, “poor as church mice; we were living on National Assistance — ‘on the pancrack’, as my grandmother called it”.

Barker, who says she has always been an avid reader, went on to study international history at the London School of Economics. After graduating in 1965, she returned to her grandparents' town to nurse her grandmother, who died in 1971. In 1969, she was introduced in a pub to David Barker, a zoology professor and neurologist 20 years her senior, who left his marriage to live with her. They had two children together, and were married in 1978, after his divorce. Their daughter Anna Ralph is now a novelist.

Barker was widowed when her husband David died in January 2009.

In her mid-twenties, Barker began to write fiction. Her first three novels were never published and, she told The Guardian in 2003, "didn't deserve to be: I was being a sensitive lady novelist, which is not what I am. There's an earthiness and bawdiness in my voice.”

Her first published novel was Union Street, which consisted of seven interlinked stories about working class English women whose lives are circumscribed by poverty and violence. For ten years, Union Street was rejected by publishers as too “bleak and depressing.” Barker then met novelist Angela Carter at a writers' workshop. Carter liked the book, telling Barker “if they can't sympathise with the women you're creating, then sod their fucking luck,” and suggested she send the manuscript to feminist publisher Virago. She did, and Virago accepted it.

Union Street was later made into a Hollywood film called Stanley and Iris, starring Robert De Niro and Jane Fonda, but Barker says the film bears little relationship to her book.

The New Statesman hailed the novel as a "long overdue working class masterpiece," and the New York Times Book Review called it “first-rate, punchy and raunchy.” As of 2003, it remained one of Virago's top sellers.

Barker's first three novels...Union Street (1982), Blow Your House Down (1984) and Liza's England (1986; originally published as The Century's Daughter) depicted the lives of working class women in Yorkshire, and are described by BookForum magazine as “full of feeling, violent and sordid, but never exploitative or sensationalistic and rarely sentimental." Blow Your House Down portrays prostitutes living in a North of England city, who are being stalked by a serial killer. Liza's England, described by the Sunday Times as a “modern-day masterpiece,' tracks the life of a working class woman born at the dawn of the 20th century.

Following publication of Liza's England, Barker felt she “had got myself into a box where I was strongly typecast as a northern, regional, working class, feminist...label, label, label...novelist. It's not a matter so much of objecting to the labels, but you do get to a point where people are reading the labels instead of the book. And I felt I'd got to that point,” she said in 1992. She said she was tired of reviewers asking “'but uh, can she do men?' -- as though that were some kind of Everest."

So, she turned her attention to the First World War, which she'd always wanted to write about due to her step-grandfather's wartime experiences, which had resulted in a scar from a bayonet wound, and that he would not speak about. This interest resulted in what is now known as the Regeneration Trilogy...Regeneration (1991), The Eye in the Door (1993), and The Ghost Road (1995)...a set of novels which explore the history of the First World War by focusing on the aftermath of trauma. The books are an unusual blend of history and fiction, and Barker draws extensively on the writings of First World War poets and W.H.R. Rivers, an army doctor who worked with traumatized soldiers. The main characters are based on historical figures, with the exception of Billy Prior, whom Barker invented to parallel and contrast with British soldier-poets Wilfred Owen and Siegfried Sassoon.

“I think the whole British psyche is suffering from the contradiction you see in Sassoon and Wilfred Owen, where the war is both terrible and never to be repeated and at the same time experiences derived from it are given enormous value,” Barker told the Guardian. “No one watches war films in quite the way the British do."

Barker told freelance journalist Wera Reusch that "I think there is a lot to be said for writing about history, because you can sometimes deal with contemporary dilemmas in a way people are more open to because it is presented in this unfamiliar guise, they don't automatically know what they think about it, whereas if you are writing about a contemporary issue on the nose, sometimes all you do is activate people's prejudices. I think the historical novel can be a backdoor into the present which is very valuable."

The Regeneration Trilogy was extremely well received by critics, with Peter Kemp of the Sunday Times describing it as “brilliant, intense and subtle," and Publishers Weekly calling it “a triumph of an imagination at once poetic and practical." The trilogy is described by the New York Times as “a fierce meditation on the horrors of war and its psychological aftermath,” and novelist Jonathan Coe describes it as "one of the few real masterpieces of late 20th century British fiction." In 1995 the final book in the trilogy, Ghost Road, won the prestigious Man Booker Prize.

Barker's biographer is Sharon Montieth.

In 1983, Barker won the Fawcett prize for fiction for Union Street. In 1993 she won the Guardian Fiction Prize for the Eye in the Door, and in 1995 she won the Booker for Ghost Road. In May 1997, Barker was awarded an honorary degree by the Open University as Doctor of the University. In 2000, she was awarded the CBE.

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