When his speech started to slur, he was diagnosed with amyotrophic lateral sclerosis – a form of motor neurone disease – aged just 21, in 1963.
Despite a bleak diagnosis, incredibly he lived with the condition for more than 50 years – before his death this morning at 76 – but since catching pneumonia in 1985 he had to have a tracheotomy which left him unable to speak.
Since then, the professor used a voice synthesiser which enabled him to control a computer screen using his cheek for data entry.
He would then have the computer read out what he has typed, in what became an iconic voice recognised around the world.
One thing continued to puzzle some, however. Many do not understand why his computer spoke with an apparent American accent, given he was born in Oxford.
The Queen even quizzed him on the matter, telling him: “Have you still got that American voice?” when meeting him at an event at St James’ Palace.
He quipped back: “Yes, it is copyrighted actually.”
But Hawking had addressed the question on his own website.
Explaining how his speech works, he wrote: “When I have built up a sentence, I can send it to my speech synthesiser.
“I use a separate hardware synthesizer, made by Speech Plus.
“It is the best I have heard, although it gives me an accent that has been described variously as Scandinavian, American or Scottish.”
He also explained that he was able to change the accent of his computer when the technology advanced, but he decided against it.
Hawking added: “My old system worked well and I wrote five books with it, including ‘A Brief History of Time’.
“It has become my trademark and I wouldn’t change it for a more natural voice with a British accent.
“I am told that children who need a computer voice want one like mine.”
Professor Stephen Hawking passed away this morning aged 76.
The English physicist died peacefully at his home in Cambridge in the early hours of the morning.
In a statement, his children Lucy, Robert and Tim said: “We are deeply saddened that our beloved father passed away today.
“He was a great scientist and an extraordinary man whose work and legacy will live on for many years.
“His courage and persistence with his brilliance and humour inspired people across the world.
“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.”
Stars have been paying tribute to his memory.