"To Kill a Mockingbird" is considered one of the great classics of 20th century American literature, and is standard reading in classrooms across the world.
Published in 1960 and drawn from Lee's own experiences as a child, it came to define racial injustice in the Depression-era South.
It tells the story of a black man wrongly accused of raping a white woman and the courageous lawyer, Atticus Finch, who defies his community to defend him.
The novel sold 30 million copies and earned huge critical acclaim, winning Lee a Pulitzer prize in 1961 and thrusting her into an avalanche of publicity.
Her fame was sealed when the novel was adapted into a Hollywood film that won three Academy Awards in 1963, including an Oscar for Gregory Peck for his portrayal of Finch, one of the best-loved characters in American fiction.
Former US president George W. Bush, who awarded Lee the Presidential Medal of Freedom, America's highest civil honor in 2007, mourned the loss of "a legendary novelist and lovely lady."
"Harper Lee was ahead of her time, and her masterpiece 'To Kill A Mockingbird' prodded America to catch up with her," he said.
"Laura and I are grateful for Harper Lee and her matchless contributions to humanity and to the character of our country," he said of his wife.
- Wit sharp as ever -
Harper Collins said Lee was not only a brilliant writer, but "an extraordinary woman of great joyfulness, humility and kindness," who lived as she wanted -- "in private -- surrounded by books and the people who loved her."
In a rare insight, the novelist admitted in 1964 she had been completely caught off guard by being catapulted into the nation's consciousness by her novel.
"I hoped for a little, but I got rather a whole lot and in some ways this was just about as frightening as the quick, merciful death I'd expected," she said, joking about her expectation the novel would be a critical flop.
For decades she stayed out of the public eye, claiming to have said all she wanted in "Mockingbird" and vowing never to publish another book.
But in 2015, she upended the literary world by publishing the unedited manuscript of "Go Set a Watchman" -- her first novel written in the 1950s which was essentially a first draft of "Mockingbird."
The manuscript was an instant popular bestseller but it was mauled by critics, and its release sparked torrid speculation that the author, who suffered a stroke in 2007, was not of sound mind.
"When I saw her just six weeks ago, she was full of life, her mind and mischievous wit as sharp as ever," said Lee's agent Andrew Nurnberg on Friday. "We have lost a great writer, a great friend and a beacon of integrity."
Born Nelle Harper Lee in April 1926, she was the youngest of four children. Her father was a lawyer and a direct descendant of Civil War general Robert E. Lee.
Lee grew up during the Great Depression in a remote village where the few available books provided the only entertainment. She never married, and books remained forever her first love.
Known as a tomboy as a child, she counted author Truman Capote among her childhood friends -- and often stood up for him when he was picked on as a sissy. She would later work as an assistant on Capote's novel "In Cold Blood," which examined a multiple killing in Kansas, and was dedicated to Lee.
- Summer backlash -
A precocious child, Lee learned to read early and had devoured all kinds of literature by the time she started school. She also showed an early flair for writing even though her family hoped she would follow her father into law.
After a spell as an exchange student at Oxford University in England, she quit law school at The University of Alabama and headed for New York in 1949 to follow her dream of being a writer.
She worked for a while as an airline reservation clerk, until one Christmas when friends gave her enough money to live for a year without working so she could concentrate on writing.
Completed before "Mockingbird," the draft she released last year as "Watchman" tells a similar tale of small-town racism but recounted from a different perspective.
While her famous novel is told through the eyes of Finch's young daughter, Scout, "Watchman" is narrated from the perspective of a grown-up Scout living in New York and coming home to the South for a troubled visit.
But critics pointed to a number of troubling inconsistencies between the two -- most notably that the hero Finch is portrayed in the manuscript as a man who harbors racist opinions.
The manuscript's release sparked a furious backlash -- partly because so little was known of Lee, who lived in a nursing home with a strictly controlled visitor list and who refused any request for interviews.
She did however quietly attend annual award ceremonies held by The University of Alabama for a writing contest inspired by her work.
Her sister, Alice, who was her gatekeeper until she died two years ago aged 103, explained in 2002 why her sister never seemed to make headway with a new work.
"I'll put it this way. When you have hit the pinnacle, how would you feel about writing more? Would you feel like you're competing with yourself?"
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