The American writer AM Homes's pitch-black new novel, May We Be Forgiven, begins with a question: "'May we be forgiven,' an incantation, a prayer, the hope that somehow I come out of this alive.

Was there ever a time when you thought – I am doing this on purpose, I am f****** up and I don't know why?"

The question – and who among us hasn't asked it of ourselves? – is posed over almost 500 pages by Harold Silver, narrator of Homes's wise, witty, weird book. This ambitious, surreal satire of suburban dystopia, sex, violence, and sibling rivalry – Cain and Abel have nothing on Harold and his brother George – began life as a short story, reveals the author of the bestselling This Book Will Save Your Life.

Speaking from the New York apartment she shares with her nine-year-old daughter Juliet, Homes reveals: "Zadie Smith asked the question that got the whole thing going." Indeed, 50-year-old Homes acknowledges her debt to Smith in this, her sixth and most unsettling novel (she's also written two short story collections and a fiercely frank memoir, The Mistress's Daughter, about having been given up for adoption at birth).

"Zadie asked me to write a story for The Book Of Other People, a benefit for one of Dave Eggers's projects. I started May We Be Forgiven but didn't finish on time. However, the story that is the first chapter of the novel – which doesn't actually have any chapters! – was chosen by William Boyd for Granta's 100th issue; then Salman Rushdie selected it for Best American Short Stories 2008," says Homes, whose first name is Amy, although even those closest to her call her "AM". The M stands for "Middle", she insists.

Even as the story was published, she kept working on it; she couldn't stop writing. She makes it sound like Topsy, that it just growed. "Exactly!" exclaims this dark-haired, blue-eyed, strong-featured woman, who is acknowledged as one of America's most significant writers and whose admirers range from Jay McInerney to Jeanette Winterson. The metamorphosis of short story into novel has happened before to Homes, with her book Music For Torching, another disturbing black comedy dealing with dysfunctional American families, which ends with a school shooting. The novel was published three weeks before the 1999 Columbine High massacre.

"That story, too, took on a life of its own," she admits. "It's surprising when that happens. In both cases – perhaps 20 pages in – there was a traditional short-story ending; a murder, say, or the burning down of a house. When you carry on writing, the difficulty is where you and the characters go from there.

"Oh sure, it's also something to do with the fact that you don't want to let certain characters go."

I didn't want to let go of those we meet in May We Be Forgiven. In addition to Harold and George there are the latter's children, Nate (12) and Ashley (11); grandparents; an aunt; FBI and CIA agents; desperate housewives; a "sex-tress"; a shrink; deli owners; secretaries; a lawyer; a gay son; an African medicine man, not to mention walk-on roles for Don DeLillo (first encountered in Starbucks, later observed buying duct tape in a shopping mall), New Yorker editor David Remnick and the brilliant American writer and cultural critic Lynne Tillman, plus several phone conversations with Julie Nixon Eisenhower, daughter of the late President Richard M Nixon.

"Lynne's a good friend; I admire her writing enormously," Homes says. "A few years ago, I saw this full-page ad in a magazine, which said, 'What Would Lynne Tillman Do?' It was apropos of nothing – I loved that, so I just took it from there. I think Don [DeLillo] is a master, particularly the way he blends fiction and history, so I'm tipping my hat to him since he lives close to where this book is set. David Remnick calls Harold [a self-effacing historian and Nixon scholar] to discuss a previously unpublished Richard Nixon short story Harold's submitted to the magazine. Oh, I had so much fun writing fiction by Nixon, who was my first 'conscious' President.

"Since I grew up in Washington DC, we'd see his family out shopping, then Watergate unfolded when I was an adolescent. It had a huge impact on me, so he's always loomed large in my mind. I did loads of research on him for the book – details of his presidency are still being released in various documents, so history is still being made.

"One thing that no American critic has picked up about this book is the number of Chinese people in it. I am very interested in the intersection of American and Chinese history and the impact of Nixon's visit to China – without that opening of relations with China, where would we be now? And, inevitably, I'm interested in whether Nixon has been forgiven."

The fast-talking Homes says she understands why I didn't want to say goodbye to her fictional characters. "For me it was an adventure to watch them grow and change, always in surprising ways since it took me so long to write – five years. They're a nice group, aren't they? It's funny, because this book has a good, hopeful end, it wasn't too bad for me to bid farewell to them, although characters do always stay with me. They feel real; I think they're all still walking around. There were worrying times when I was writing this book, though, when I wasn't at all sure how it was going to end, which was a big concern. Now I'm happy because the ending is redemptive."

So, to begin at the beginning. The novel opens with Thanksgiving dinner at George's home in New York's prosperous Westchester County. As he helps to clear up, Harold watches his older, powerful TV executive brother, who has a history of psychotic outbursts, sitting at the head of the table, picking turkey out of his teeth and talking about himself. The edges of his fingers "dipping into unnameable goo – cranberry sauce, sweet potatoes, a cold pearl onion, gristle". Harold confesses: "With every trip back and forth from the dining room to the kitchen, I hated him more."

Three months later George drives through a red light, killing two people, leaving their son orphaned. While George is in a psychiatric ward, Harold and his sister-in-law Jane embark on an affair. George escapes from hospital, discovers them in bed together and bashes Jane's head in with a lamp – and that's just the first 15 pages.

With George locked up again, Harold moves into his house, takes care of his niece and nephew and the family pets, starts trawling the internet for sex after his Chinese wife dumps him, and writes his magnum opus, working title, While We Were Sleeping: The American Dream Turned Nightmare – Richard Nixon, Vietnam And Watergate: The Psychogenic Melting Point.

The American dream turned nightmare has long been Homes's theme – telling Homes's truths, so to speak, about the meltdown of the American family. Truly, there is no place like Homes, although we're definitely in John Cheever territory. He's a key literary figure for her, although she discloses that, unlikely as it may seem, a 1400-page fictionalised account of the CIA by Norman Mailer, Harlot's Ghost (1991), also influenced May We Be Forgiven. "He's never been one of my favourite writers but this book is incredible," she says

Homes, who grew up in the affluent suburbs of Chevy Chase, Washington DC, raised by left-leaning intellectual adoptive parents, also quotes her mentor Grace Paley, who taught her about "writing the truth according to the character". Perhaps this is why Homes so effortlessly captures the male voice. Indeed, she once said at an event in New York that she may have an "old-man psyche", confessing to having dressed up as Willy Loman for Hallowe'en when in fourth grade.

"I don't by nature write autobiographically," she says. Intensely private, it's astonishing that she chose to write a memoir as revelatory as The Mistress's Daughter. "The story was so peculiar and emotionally strange I had to write it. I was finding things out about myself and my family, although I am not that interested in myself and I never expose myself – literally – in print," she told me when we met in 2007.

After graduating from Sarah Lawrence College, New York, Homes attended the renowned Iowa Writers Workshop in Iowa City and has written and produced for the TV series, The L Word. She and Juliet – she refuses to say whether she has a partner – live in the Hamptons as well as in New York City. She's recently worked on a major TV series for HBO, The Hamptons, although it's presently on hold. She also lives and writes on and off in Los Angeles at the gorgeous Chateau Marmont Hotel on Sunset Boulevard (Greta Garbo, John Lennon and Jim Morrison hung out there) and often stays at Yaddo, the writers' colony in Saratoga Springs, run by Glaswegian Elaina Richardson.

"Without Elaina and her staff, I'd never write anything – I feel so tended and cared for there," she concludes.

May We Be Forgiven by AM Homes is published by Granta, priced £16.99.