The Man Booker International Prize was started in 2016 to celebrate fiction that has been translated into English from around the world.
Ms Tokarczuk's novel combines tales of modern-day travel with the story of a 17th century anatomist who dissected his own amputated leg and the journey of composer Frederic Chopin's heart from Paris to Warsaw after his death. However, 2014 was permitted to nominate English-speaking authors from other countries. She will split the cash with translator Jennifer Croft.
"Tokarczuk is a writer of wonderful wit, imagination and literary panache", said head judge Lisa Appignanesi, adding, "I think picking up "Flights" will be an experience for anyone".
"We really felt this is a prize that has an interventionist quality - it allows writers to be better known in Britain, and in the English language, than they have been previously", said Appignanesi.
Poland's Olga Tokarczuk wins Man Booker International Prize
Her first book, "The Journey of the People of the Book", was published in 1993. She won the award again in 2015 for The Books Of Jacob, a novel about the 18th-century Polish-Jewish religious leader, Jacob Frank. A film adaptation of Drive Your Plow Over the Bones of the Dead - titled Pokot (Spoor) - was denounced by a Polish news agency as "a deeply anti-Christian [work] that promoted eco-terrorism".
The panel, which included German poet and translator Michael Hofmann, author Hari Kunzru, journalist Tim Martin and author Helen Oyeyemi, said Flights was "also about never leaving your body, which itself is in movement and is going to die". Since then, her bestselling books have been translated into more than 25 languages. Tokarczuk and Croft were presented the award at a ceremony in Victoria and Albert Museum here on late Tuesday night.