He died peacefully at his home in the British university city of Cambridge in the early hours of Wednesday.
“We are deeply saddened that our beloved father passed away today,” his children Lucy, Robert and Tim said in a statement.
Hawking’s formidable mind probed the very limits of human understanding both in the vastness of space and in the bizarre sub-molecular world of quantum theory, which he said could predict what happens at the beginning and end of time.
His work ranged from the origins of the universe, through the tantalizing prospect of time travel to the mysteries of space’s all-consuming black holes.
“He was a great scientist and an extraordinary man whose work and legacy will live on for many years,” his family said. “His courage and persistence with his brilliance and humor inspired people across the world.”
The power of his intellect contrasted cruelly with the weakness of his body, ravaged by the wasting motor neuron disease he developed at the age of 21.
Hawking was confined for most of his life to a wheelchair. As his condition worsened, he had to resort to speaking through a voice synthesizer and communicating by moving his eyebrows.
The disease spurred him to work harder but also contributed to the collapse of his two marriages, he wrote in a 2013 memoir “My Brief History.”
In the book he related how he was first diagnosed: “I felt it was very unfair - why should this happen to me,” he wrote.
“At the time, I thought my life was over and that I would never realize the potential I felt I had. But now, 50 years later, I can be quietly satisfied with my life.”
Hawking shot to international fame after the 1988 publication of “A Brief History of Time”, one of the most complex books ever to achieve mass appeal, which stayed on the Sunday Times best-sellers list for no fewer than 237 weeks.
He said he wrote the book to convey his own excitement over recent discoveries about the universe.
”My original aim was to write a book that would sell on airport bookstalls,” he told reporters at the time. “In order to make sure it was understandable I tried the book out on my nurses. I think they understood most of it.”
He was particularly proud that the book contains only one mathematical equation - relativity’s famous E=MC squared.
“We have lost a colossal mind and a wonderful spirit,” said Tim Berners-Lee, the inventor of the World Wide Web. “Rest in peace, Stephen Hawking.”
Hawking’s popular recognition became such that he appeared as himself on the television show “Star Trek: Next Generation” and his cartoon caricature appeared on “The Simpsons”.
A 2014 film, The Theory of Everything, with Eddie Redmayne playing Hawking, charted the onset of his illness and his early life as the brilliant student grappling with black holes and the concept of time.