A sell-out crowd of around 720 people was in the Apollo Theatre watching "The Curious Incident of the Dog in the Night-time" when ornate masonry and rigging fell some five storeys onto their heads.
Witnesses said they heard creaking noises in the 112-year-old theatre before the collapse but thought it was part of the show, which is one of London's most popular and was packed with families the week before Christmas.
Rescuers commandeered three iconic red London double-decker buses to transport the wounded, while London's normally tourist-thronged "Theatreland" was brought to a stunned halt.
Paramedics initially said 88 people were wounded but later revised the number downwards to 76. Seven were seriously injured, another 51 "walking wounded" were taken to hospital with minor injuries and the rest were treated at the scene.
"A section of the theatre's ceiling collapsed onto the audience who were watching the show. The ceiling took parts of the balconies down with it," senior firefighter Nick Harding told reporters.
"In my time as a fire officer I've never seen an incident like this. I imagine lots of people were out enjoying the show in the run-up to Christmas."
Witnesses told of terror inside the Edwardian-era theatre, which has three tiers of balconies, the uppermost of which is said to be the steepest in London.
People were crying in shock and coughing because of the dust as they fled to safety.
Desmond Thomas, 18, part of a school party watching the show, said they heard noises before the accident.
"Maybe 10 minutes into the performance we heard a tap-tap noise, we thought it was rain," he told AFP.
"There was a crack and then it suddenly seemed to get bigger and suddenly it collapsed. The next thing we knew the whole theatre filled with dust and smoke."
A thunderstorm had hit London in the hour before the incident.
Simon Usborne, a journalist for The Independent newspaper who was watching the show, said there was "chaos".
"Loud bangs, cracks. Thought was part of show then whole interior of theatre filled with curtain of dark grey dust and debris, falling on heads of anyone not sheltered," he tweeted afterwards.
"People emerging soon after bloodied - children crying - family show - people dumbfounded."
Prime Minister David Cameron said he was being kept updated on the incident and was "grateful for the fast work of the emergency services in helping the injured".
Police said they were investigating the cause of the incident alongside structural engineers from the local council.
"There is no suggestion at this stage that this was as a result of a criminal act, however, at this stage we of course are keeping an open mind," said Chief Superintendent Paul Rickett.
A fire brigade cherry picker could be seen stretching high over the theatre after the incident.
Several people were stretchered out of the theatre, while others with bandages on their heads were being treated in triage centres set up in the lobbies of the nearby Gielgud and Queen's theatres.
"In the finest traditions of Theatreland, they very quickly rallied around," said fire brigade spokesman Graham Ellis.
Ellis said that "heavy ornate plaster" had fallen from the roof onto theatregoers in the circle, dress circle and stalls.
Audience member James Kearney, who was given a ticket to the show as a present, told AFP there were "people with blood on their heads in shock" behind them.
Kearney's companion Dee Stephenson said there was so much dust afterwards they had to feel their way out.
"Everybody was in a trance-like state. A lot of people were in absolute shock," Stephenson told AFP.
"We were extremely fortunate."
Based on an award-winning novel by Mark Haddon, "The Curious Incident of the Dog in the Night-time" has been running in London since August 2012.
Haddon said on Twitter that the incident was "horrifying" and that he was "hugely relieved that no one died".
The current owner of the Apollo, Nimax Theatres, said the ceiling collapse was a "shocking and upsetting incident".
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