Saunders also received a designer-bound edition of his book and a further 2,500 pounds for being shortlisted.
Judges praised the "utterly original" work and said it was "deeply moving".
Lincoln In The Bardo tells the story of Abraham Lincoln's grief after the death of his young son and is set in a graveyard over a single night.
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In his acceptance speech, Saunders called the prize a wonderful honor and thanked his wife Paula who has encouraged him to continue the book when he suffered from frustration during writing. Or do we take that ancient great leap of faith and do our best to respond with love?
"It is a room full of believers in the word, in beauty and ambiguity and in trying to see the other person's point of view, even when that is hard".
The 58-year-old writer, who had been favourite to win, was presented with the prestigious literary award and STG50,000 ($A84,000) prize during a ceremony at the Guildhall in central London, attended by the Duchess of Cornwall.
Founded in 1969 and originally open only to writers from Britain, Ireland and the Commonwealth, the Booker expanded in 2014 to include all English-language authors.
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Previous year the American writer Paul Beatty won the prize for his book Sellout.
The judges of The Man Booker Prize are chosen from a wide range of disciplines including critics, writers, academics, poets, politicians, actors and "all with a passion for quality fiction".
The other Booker finalists are Scottish novelist Ali Smith's Brexit-themed "Autumn;" British-Pakistani writer Mohsin Hamid's migration saga "Exit West;" and "Elmet, " debut British novelist Fiona Mozley's story of a fiercely independent family under threat.
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