Propelled to superstardom by his 1988 book "A Brief History of Time", which became an unlikely worldwide bestseller, Hawking dedicated his life to unlocking the secrets of the Universe.
His genius and wit won over fans from far beyond the rarified world of astrophysics, earning comparisons with Albert Einstein and Sir Isaac Newton.
Hawking died peacefully at his home in the British university city of Cambridge in the early hours of Wednesday morning.
We are deeply saddened that our beloved father passed away today," professor Hawking's children, Lucy, Robert, and Tim said in a statement carried by Britain's Press Association news agency.
"He was a great scientist and an extraordinary man whose work and legacy will live on for many years."
Hawking defied predictions, he would only live for a few years after developing a form of motor neurone disease in his early 20s.
The illness gradually robbed him of mobility, leaving him confined to a wheelchair, almost completely paralysed and unable to speak except through his trademark voice synthesiser.
"His courage and persistence with his brilliance and humour inspired people across the world," his family said.
"He 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."