In a dramatic start to the London ceremony, six Paralympians and former competitors — including Baroness Tanni Grey-Thompson — were flown into the stadium in gold wheelchairs.
Accompanying the athletics star were fellow Paralympians Robert Barrett, Kay Forshaw, Tony Griffin, Ian Rose and Marc Woods.
Professor Stephen Hawking was one of the unexpected stars of the show — which heralded the start of the 11-day contest.
Prof Hawking opened the event, speaking in his distinctive synthesised voice of the quest for understanding the universe.
Amid fireworks, an aeroplane blazing golden sparks and dancing performers was a celestial sphere, surrounded by 600 umbrella-wielding volunteers.
The show started with a flypast by Aerobility, a British charity which trains disabled people to become pilots.
The sphere ignited the ‘big bang’, which triggered fireworks around the Olympic stadium.
In a show which organisers described as being “profoundly about science and humanity”, Prof Hawking acted as a guide to Miranda, from William Shakespeare’s The Tempest, who was central to the show.
Actor Sir Ian McKellen, meanwhile, starred as another character from the play, Prospero.
Six-London based choirs performed Principia, a specially-composed piece by Greenwich-based composer Errollyn Wallen.
Prof Hawking said the Paralympic Games was about transforming people’s perception of the world.
He said: “We are all different. There is no such thing as a standard or run-of-the-mill human being but we share the same human spirit.
“What is important is that we have the ability to create.”
In a statement released in advance of the opening ceremony, The Queen said the Games would be returning to the country where they first began, more than 60 years ago.
Earlier, the Paralympic Flame was greeted by large crowds as it made its way past some of the most famous landmarks in the capital.
The torch visited London Zoo, Regent Street, Trafalgar Square and Whitehall on its journey to the Olympic Stadium in Stratford.
There are two Northern Ireland athletes in the GB team, including 200m runner Sally Brown who has the potential to upset the odds and take top spot on the podium at the age of just 17.
As the Paralympians made their way through the stadium, flagbearer Cathal Miller led the Irish team out to a rapturous reception.
The 39-year-old cyclist, from Artane in Dublin, followed in boxing hero Katie Taylor's footsteps by hoisting the Irish flag aloft. He had been elected as standard bearer by the 49-strong team.
Their joy and excitement were clear to see as they performed a lap of the Olympic Stadium, waving their mini-flags and soaking up the atmosphere.
Six Northern Ireland competitors feature in the Irish team.
Before the opening ceremony began, Belfast was already getting into the Paralympic spirit at City Hall with stilt walkers, jugglers, musicians and dancers kicking off the local celebrations.
Lord Mayor Gavin Robinson encouraged people to come down and watch the games on the big screen until 10pm every night. “Over the course of the next two weeks, we hope people will come down and support the Paralympians,” he said.