The Theory of Everything became the title of the 2014 film that charted Professor Hawking's early life and how he came to terms with amyotrophic lateral sclerosis, the crippling disease that gradually paralysed him.
His 1988 book "A Brief History of Time" sought to explain to non-scientists the fundamental theories of the universe and it became an worldwide bestseller, bringing him global acclaim. "May his soul rest in peace", the prime minister said on Twitter.
The illness gradually robbed him of mobility, leaving him confined to a wheelchair, nearly completely paralysed and unable to speak except through his trademark voice synthesiser. "He was a great scientist and an extraordinary man whose work and legacy will live on for many years", Hawking's children said in a statement.
"I try to lead as normal a life as possible, and not think about my condition, or regret the things it prevents me from doing, which are not that many", he wrote on his website.
But it was his ability to explain the most complex of ideas in terms that anyone could understand that brought fame far beyond the scientific community.
As he was preparing to marry his first wife, Jane, in 1964 his doctors gave him no more than two or three years of life.
One of his most famous accomplishments came in his research on black holes, showing that small amounts of radiation could escape their gravitational pull.
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A previous holder of the prestigious post was the 17th-century British scientist Isaac Newton. After that, he tied the knot with his nurse, Elaine Mason, with whom Hawking spent his next 11 years.
Hawking said making the first moves into space would "elevate humanity" because it would have to involve many countries. Hawking authored seven books, co-authored nine others, and was the recipient of dozens of scientific, academic, and other awards including The Albert Einstein Award, The Hughes Medal, and the Presidential Medal of Freedom.
Pop culture fans should recognise Hawking from his guest spot (as his own hologram) in the Star Trek: The Next Generation episode, "Descent", or his appearances on The Simpsons, Futurama, and others.
"His passing has left an intellectual vacuum in his wake", said Neil deGrasse Tyson.
"Stephen once said, 'It would not be much of a universe if it wasn't home to the people you love.' We will miss him forever".
Hawking's seminal contributions continued through the 1980s.
Former US Ambassador to the UN Samantha Power underlined Hawking's kind heart in addition to his brilliant mind.