"Clearly, there will be questions in the course of the next few days and weeks about how it happened and what we can do to make sure that it doesn't happen again," the London mayor said on a visit to the scene.
"There are all sorts of questions that people are asking now, about tall buildings, about lighting, about fog, about the usage of Battersea heliport. And those are very understandable questions in these circumstances because people will naturally want to know we are doing our level best to make sure that London is protected from aviation accidents of this kind."
He said the matters were being investigated by the Civil Aviation Authority (CAA) and it "would be wrong for me to pre-empt any of that".
Johnson described what he saw as "a tragic scene of the wreckage of a carbonised helicopter and, of course, a great deal of damage done to an adjacent building. It doesn't take a great deal to imagine what could have happened had that helicopter crashed into a bus or a heavily occupied building."
It could "have been much worse", he said, adding it was "immensely reassuring" that the emergency services got to the scene so quickly and did "such a fantastic job throughout the day".
"There will be a great deal of interest into how we are organising the flights into the Battersea heliport. Are there adequate protections? That's exactly the kind of thing that you would expect us to be looking into now. But, before we get into that, I think it is really right to see what the CAA comes up with."
The prime minister, David Cameron, said the rules for helicopter flights over central London would need to be carefully examined.
Speaking at prime minister's questions, he agreed with the Vauxhall MP, Kate Hoey, on the need to look into the use of helicopters in the capital in light of its changing skyline and the increasing number of skyscrapers.
"I think the point she makes about the rules for helicopter flights and indeed other flights over our capital city, I'm sure they will be looked at as part of the investigations that will take place."
Speaking in the Commons, he paid tribute to the "brave and professional" response of the emergency serves to the crash.
"I think everyone can see from the terrifying pictures on our televisions this morning just how quickly the emergency services responded and how brave and how professional they were in the way they responded," he said.
Earlier, his official spokesman told a regular media briefing in Westminster that the prime minister had been informed of the incident shortly after it happened and was "very saddened to learn of the fatalities and injuries in this incident". The crash happened less than a mile down the river Thames from the Houses of Parliament and its aftermath was witnessed by a number of MPs.
David Morris, the Conservative MP for Morecambe and Lunesdale, who has a flat just yards from the crash site, said: "I was reading my science and technology papers at around 8am when I heard a loud bang. It became apparent that a helicopter had crashed around 100-150 yards away from my flat … I am incredibly shaken. My thoughts are with those directly involved."
The Loughborough Conservative MP Nicky Morgan was walking towards Vauxhall at the time and saw thick black smoke. "Within a minute there were sirens, so you felt that the emergency services were immediately reacting, which was comforting. It is a terrible, unexpected tragedy. I wondered if it was a bomb explosion," she told BBC News.
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