The extravaganza, directed by Bradley Hemmings and Jenny Sealey, was billed as a voyage across "a sea of ideas" including Isaac Newton's discovery of gravity, which all Earth-bound athletes strive against. The show included 73 deaf and disabled professional performers and 68 disabled people among its 3,250 volunteers.
The gala opened with a look at the Big Bang considered the beginning of the universe as a glowing sphere turned the stadium into a giant nebula.
As the athletes entered, they were welcomed by a global music mash-up by local DJs followed by blind soprano Denise Leigh singing the Paralympic tribute song "Spirit in Motion."
In a nod to the famously erratic British weather, umbrellas were a central theme. Seeing performers with no legs beneath the knee doing aerial flips carrying umbrellas could inspire the most ardent couch potato.
And of course, this being Britain, the words of Shakespeare once again were to make an appearance, with both Miranda of "The Tempest" and British actor Ian McKellen announcing that "the greatest adventure is what lies ahead."
That, over the next 11 days, includes Paralympic athletes competing in 20 sports, including archery, cycling, rowing, equestrian, sailing, sitting volleyball, wheelchair rugby, wheelchair tennis and wheelchair basketball.
In the ceremony, Hawking directed the fictional Miranda to "be curious" and the stadium was transformed into a giant blinking eye. Along her travels, the curious Miranda was to navigate a maze to find an apple and everyone in the stadium was given the fruit as they entered and encouraged to take a bite out of the fruit when she did.
Other performers included soprano Elin Manahan Thomas, Beverley Knight, the British dance group Flawless and six London-based choirs.
Outside the stadium, hundreds of performers cheered, sang and danced as the Paralympians lined up to enter. Jason Kajdi, 18, of south London did huge splits with bouncy legs that resembled the "Cheetah" prosthetic limbs used by Olympic sprinter Oscar Pistorius.
"Never used these before this," he admitted. "They are brilliant fun but hard work!"
Authorities, meanwhile, promised to provide "a grand and global stage" for a games that everyone will remember.
Queen Elizabeth II said the nation looked forward to "celebrating the uplifting spirit which distinguishes the Paralympic Games from other events."
She was accompanied by her grandson, Prince William, his wife Kate, and Prime Minister David Cameron.
Sebastian Coe, chief of the London organizing committee, planned to give a big welcome home "to a movement that shows what sport is all about."
The Paralympic movement tracks its beginnings to the vision of Dr. Ludwig Guttmann, who in 1948 organized an archery competition for 16 injured patients at Stoke Mandeville Hospital in Britain.
Wednesday's ceremony was to conclude with Miranda breaking a glass ceiling just as Paralympians must break through their own barriers showering the stadium in pixels.
Society, too, was encouraged to break its old-fashioned perceptions of what disabled people can and cannot do.
"The Paralympic Games have inspired us to make London a more inclusive and welcoming city, to shift perceptions of disability and break down barriers in society," London Mayor Boris Johnson said.