Emergency services were called to the Apollo Theatre on Thursday evening after a section of the ceiling collapsed and fell onto theatregoers.
The venue, which is situated on Shaftesbury Avenue, is home to award-winning play The Curious Incident of the Dog in the Night-time.
Initial reports on Twitter were that a balcony had collapsed, but it was since reported that part of the roof came down during the performance, just prior to the interval.
"People were looking up in a bewildered way when the roof came down, wondering if it was part of the show," an eyewitness told BBC News. "Those close to the emergency exit managed to get out, though others were trapped."
The ambulance services reported at 9.30pm there were 65 casualties, including walking wounded. Latest estimates indicate that there are seven seriously injured people.
The Apollo has 775 seats over four levels. It opened its doors in 1901 and is currently owned by Nimax Theatres.
The last major ceiling collapse in the West End was at the Shaftesbury Theatre in 1973, in which plasterwork fell onto the stage and audience during a performance of Hair.
The scene inside the Apollo after the roof came down was described as "chaos".
"I was hit on the head by a piece of masonry," an audience member told the BBC. "We thought it was part of the show at first, then we saw all the actors looking up and pointing, looking horrified."
Speaking to Sky News, a theatregoer who was sitting in the second row of the stalls described the roof as "landing on people".
"There was a lady who was in a lot of shock and had a lot of debris over her and a cut head," he added.
The section of plaster roof that came down was said to be ten metres in circumference. One theatregoer reported seeing sparks from the ceiling.
A group of audience members reportedly went back inside the venue to help following the evacuation. Emergency services were on the scene within minutes and Shaftesbury Avenue was cordoned off.
The neighbouring Gielgud and Queen's Theatres were used as emergency treatment centres.
Nick Harding of the London Fire Brigade said: "We believe around 720 people were in the theatre at the time. 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.
"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. My thoughts go out to all those affected."
Prime Minister David Cameron tweeted: "I've been updated regularly on the Apollo incident. I'm grateful for the fast work of the emergency services in helping the injured."
Mayor of London Boris Johnson said: "Thank you to everyone involved in the emergency operation at the Apollo theatre tonight – incredible response in very difficult conditions."
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