The book, which traces the disease from the first recorded mastectomy in 500 BC to today's cutting edge research, was the only non-fiction title on the shortlist, and beat four novels for the award worth 10,000 pounds.
The chair of judges, Lisa Allardice, editor of Guardian Review, said Mukherjee's "anthropomorphism of a disease" was a "remarkable and unusual achievement". Mukherjee is assistant professor of Medicine at Columbia University.
She said, "In the end it came down to a very difficult decision between a first novel and a first book of tremendous research. They were so different -- both incredibly impressive achievements in their own rights, but in the end the Mukherjee was felt to be the more original".
Allardice added, "He has managed to balance such a vast amount of information with lively narratives, combining complicated science with moving human stories. Far from being intimidating, it's a compelling, accessible book, packed full of facts and anecdotes that you know you will remember and which you immediately want to pass on to someone else."
The other four books on the shortlist were: Pigeon English (Stephen Kelman), Down The Rabbit Hole, (Juan Pablo Villalobos), The Collaborator (Mirza Waheed) and The Submission (Amy Waldman).
Author and academic Sarah Churchwell -- who joined Allardice on the judging panel for the Guardian award along with the authors David Nicholls and Antonia Fraser, Stuart Broom of Waterstone's and the Guardian's deputy editor
Katharine Viner -- said Mukherjee had "marshalled an immense amount of material into a readable and inspiring story" and that the result is "a gripping, enlightening read about the nature of illness and our battle against what begins to look like mortality itself".
Mukherjee, who is writing a second book, said it was "a great and distinct honour" to win the Guardian prize. He said, "You never write books to win awards -- they are immensely gratifying but unexpected. In recognising The
Emperor of All Maladies, the judges have also recognised the extraordinary courage and resilience of the men and women who struggle with illness, and the men and women who struggle to treat illnesses. I am delighted and honoured to join a formidable list of writers and scholars -- Zadie Smith, Alexandra Harris, Petina Gappah, and Alex Ross among them."