"He was a great scientist and an extraordinary man whose work and legacy will live on for many years," his three children, Lucy, Robert and Tim, said in a joint statement.
"His courage and persistence, with his brilliance and humor, 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."
Neil deGrasse Tyson, another scientist who has made great strides in popularizing the field among the wider public, paid tribute to the Cambridge academic with a typically tongue-in-cheek physics joke.
"His passing has left an intellectual vacuum in his wake," the astrophysicist wrote on Twitter.
"But it's not empty. Think of it as a kind of vacuum energy permeating the fabric of spacetime that defies measure. Stephen Hawking, RIP 1942-2018."
NASA's official Twitter account marked his death with a moving tribute.
"Remembering Stephen Hawking, a renowned physicist and ambassador of science. His theories unlocked a universe of possibilities that we & the world are exploring," it said.
"May you keep flying like superman in microgravity, as you said to astronauts on @Space_Station in 2014."
The European Space Agency wrote of how Hawking "showed us there are no limits to achieving our dreams" alongside a photograph of the physicist enjoying the weightlessness of a zero-gravity flight in 2007.
World and industry leaders also noted his passing. Indian Prime Minister Narendra Modi tweeted his condolences.
"Professor Stephen Hawking was an outstanding scientist and academic. His grit and tenacity inspired people all over the world. His demise is anguishing. Professor Hawking's pioneering work made our world a better place. May his soul rest in peace."
China's Ministry of Foreign Affairs also offered a salute to Hawking, with spokesperson Lu Kang recalling the time the physicist "once insisted and finally realized his desire to ascend to the Great Wall with the help of an assistant."
Google CEO Sundar Pichai simply wrote: "The world has lost a beautiful mind and a brilliant scientist. RIP Stephen Hawking."
Former colleagues from the world of academia and research also posted memories of Hawking.
Egyptologist and "space archaeologist" Sarah Parcak recalled how one encounter between the two almost came to a messy end.
"I nearly killed him, and he me, 15 years ago, when his wheelchair shot out between two parked cars at Cambridge, and I was on my bike," she tweeted. "I swerved at the last moment. 100% his fault. God bless you and RIP."
David Wands, director of the Institute of Cosmology and Gravitation at the University of Portsmouth in southern England and former student at Cambridge, recalled how crowds turned out to listen to Hawking lecture.
"He was a huge inspiration to me personally when I was a student at Cambridge," Wands said. "At the time he was just writing the first draft of his book 'A Brief History of Time' and he gave a series of lectures for undergraduates. The lectures were optional, not part of any exam, but we turned out in droves to hear him speak. Sitting on the steps in the lecture theater to hear the words of the great man."
Martin Rees, emeritus professor of cosmology and astrophysics at the University of Cambridge, met Hawking when they were both students in 1964.
"Astronomers are used to large numbers. But few numbers could be a large as the odds I'd have given, back in 1964 when Stephen received his 'death sentence,' against witnessing this uniquely inspiring crescendo of achievement sustained for more than 50 years," Rees said. "Few, if any, of Einstein's successors have done more to deepen our insights into gravity, space and time.
"His name will live in the annals of science; millions have had their cosmic horizons widened by his best-selling books; and even more, around the world, have been inspired by a unique example of achievement against all the odds -- a manifestation of amazing will power and determination," he added.
Stars across the globe also paid tribute to Hawking on Wednesday.
Eddie Redmayne, who won an Academy Award for his transformation into Hawking for the 2014 film "The Theory of Everything" said in a statement: "We have lost a truly beautiful mind, an astonishing scientist and the funniest man I have ever had the pleasure to meet. My love and thoughts are with his extraordinary family."
Singer Cher reminisced on Twitter about an "amazing" lunch the pair shared before adding "RIP Dear." And American Idol judge Katy Perry described the loss as "a big black hole in my heart hours before Pi day."
Oscar-nominated screenwriter and actor Kumail Nanjiani also hailed Hawking's work, posting: "RIP Stephen Hawking. Genuinely very sad to hear that. If you haven't, read A Brief History of Time. It'll make the world feel more amazing and beautiful and strange. it'll also make you feel smart and stupid all at once."
"Star Trek" star and LBGT icon George Takei noted on Twitter: "One of the greatest minds our species has ever produced is returned to the stars. It is a great loss to the scientific community, and a hero to so many more."
Hawking also made multiple appearances guest-starring as himself on the top-rated US nerd comedy "The Big Bang Theory," which posted a snap of the beloved physicist surrounded by the cast.
Huffington Post reporter Ashley Feinberg also recalled his sense of humor.
"One of my favorite things about Stephen Hawking is that he was mean to all the right people," she posted, along with text recounting how he would "enjoy running over the toes of people he didn't like" with his wheelchair, including an anecdote of allegedly doing exactly that to Prince Charles.
Citing a biography of the scientist, the passage added that "one of Hawking's regrets in life was not having an opportunity to run over (former British Prime Minister) Margaret Thatcher's toes."
"Absolutely heartbroken at the news of Stephen Hawking's passing. He was a huge inspiration to me as a teen when I was in and out of wheelchairs from my illness -- seeing him keeping on doing science kept me going."
CNN's Serenitie Wang contributed to this report from Beijing.