A record 4 200 athletes from 166 countries will be in the British capital, with the 11-day Games a near sell-out and expected to be watched by an estimated global television audience of four billion people.
Britain is considered the birthplace of the Paralympic movement, after World War II veterans with spinal injuries competed in archery events at Stoke Mandeville in southern England in 1948, 12 years before the first official Games in Rome.
The International Paralympic Committee (IPC) said that history, a desire to see more elite sport after a successful Olympics, increased media coverage and sponsorship have combined to drive up interest and awareness.
"There's a fantastic buzz in the air, waiting for it to kick off and people talking about it," IPC president Philip Craven said before next Wednesday's opening ceremony.
China held the last Paralympics in Beijing in 2008 and did much to raise the Games' profile.
The previous hosts won 211 medals, including 89 gold, and will be looking to replicate that success this time round.
But challenging them will be the current hosts, who came third in the Olympics medal table, galvanising wide support for the Games across the country and lifting a national mood hit by lingering economic woes.
ParalympicsGB have been set a minimum target of 103 medals from at least 12 different sports – one better than in Beijing – and to match their second-place finish four years ago.
For the home team, hopes are highest for athletes like Jonnie Peacock, who in June set a new T44 100m record of 10.85secs and is expected to challenge Oscar Pistorius for gold in the showpiece track event.
With Pistorius' long-standing rival Jerome Singleton, of the United States, and a host of other lightning-fast sprinters likely to line up in the final, organisers even predict that all eight runners could dip under 11secs.
Among the wheelchair racers, Britain's David Weir, the T54 800m and 1 500m champion four years ago, is set to renew his rivalries with Australia's Kurt Fearnley and Swiss world record holder Marcel Hug.
Decade at the top
In the pool, Ellie Simmonds has become a poster girl for the Games after winning two golds in Beijing aged just 13.
But like Pistorius – the first double amputee to compete in the Olympics and the Paralympics' biggest star – there are other big names.
South Africa's Natalie Du Toit is retiring after a decade at the top, while Matthew Cowdrey – an eight-time gold medallist – needs just three more golds to surpass athlete Tim Sullivan to become Australia's most successful Paralympian.
London will also see veteran medallists like shooter Jonas Jacobsson, dressage specialist Lee Pearson and Dutch wheelchair tennis player Esther Vergeer going for gold again alongside first-time athletes from smaller nations.
Now 47, Sweden's Jacobsson has competed in eight Paralympics and has 16 golds; Pearson, of Britain, has won gold at every Games since Sydney 12 years ago; while Vergeer won in 2000, 2004 and 2008 and is unbeaten in over 450 matches.
The US Virgin Islands will have their first ever Paralympian in the shape of rider Lee Frawley, while North Korea make its debut in the competition with swimmer Rim Ju Song.
Some 200 athletes with intellectual disabilities will also compete for the first time since Sydney and a scandal involving the eligibility of Spain's basketball team.
And while every athlete has as much determination to overcome adversity as talent and skill, few have as remarkable a backstory as Martine Wright, who lost her legs in the 2005 suicide attacks in London – a day after the city was awarded the Games.
She will be a member of Britain's sitting volleyball team.
London organising committee chairperson Sebastian Coe has repeatedly maintained that the Paralympics and the Olympics are two equal parts of the same event.
"We want to change public attitudes towards disability, celebrate the excellence of Paralympic sport and to enshrine from the very outset that the two Games are an integrated whole," he said. – Sapa-AFP