Pratchett, who wrote more than 70 books, including those in his "Discworld" series, had been diagnosed with a rare form of Alzheimer's disease in 2007.
A statement on the website announced the news of his death at home Thursday with "immeasurable sadness."
"I was deeply saddened to learn that Sir Terry Pratchett has died. The world has lost one of its brightest, sharpest minds," said Larry Finlay, managing director at Transworld Publishers.
"In over 70 books, Terry enriched the planet like few before him. As all who read him know, 'Discworld' was his vehicle to satirize this world: He did so brilliantly, with great skill, enormous humor and constant invention."
Pratchett continued to write following his diagnosis, completing his last book, a new Discworld novel, in the summer of 2014.
Revealing his illness in 2007, the author -- who had a strong following among fans of fantasy fiction -- said he had been diagnosed with "a very rare form of early onset Alzheimer's," which he described as "an embuggerance."
He said then, "Frankly, I would prefer it if people kept things cheerful, because I think there's time for at least a few more books yet."
According to Thursday's statement, he had posterior cortical atrophy, a progressive degenerative condition involving the loss and dysfunction of brain cells, particularly at the back of the brain.
The last posts on his verified Twitter account
, run by Pratchett with close friend Rob Wilkins, give a poignant farewell -- and have already been retweeted thousands of times.
"AT LAST, SIR TERRY, WE MUST WALK TOGETHER," the first tweet in the series reads -- an apparent reference to Death, a recurring and generally sympathetic character in the Discworld books, who always speaks in ALL CAPS.
"Terry took Death's arm and followed him through the doors and on to the black desert under the endless night.
Jeremy Hughes, chief executive of the Alzheimer's Society, a charitable organization, said Pratchett -- who spoke out publicly about his condition and called for greater funding for Alzheimer's research -- had "fundamentally changed the way dementia is seen and understood."
"His vehement determination to reduce the stigma of dementia meant he helped drag it out of the shadows -- kicking and screaming at times," he said.
"Shouting from the rooftops about the absurdity of how little funding dementia research receives, and fighting for good quality dementia care, he was and will remain the truest of champions for people with the condition."
Pratchett was also a patron of the British Humanist Association, which paid tribute Thursday to the humor and dedication with which the author "turned his suffering into a positive campaign."
Pratchett, who began writing while a provincial newspaper journalist in the 1960s, became a full time writer in 1987 and received the Order of the British Empire "for services to literature" from Prince Charles in 1998.