Pro-Union campaigners had "seven months to save the most extraordinary country in history", the PM argued.
In an emotional speech, he spoke about his Scottish ancestry and said the referendum was "personal" to him.
Mr Cameron, who chose to make his biggest intervention in the referendum debate so far at the Olympic Park in East London, said he planned to make his argument in Scotland too. He said he had chosen the Olympic Park as a venue for his speech because he wanted to send a message to everyone, adding "all 63 million of us are profoundly affected".
"That's why this speech is addressed not to the people of Scotland, but to the people of England, Wales and Northern Ireland. We would be deeply diminished without Scotland. This matters to all our futures. And the UK has a voice."
Some people had advised him not to take part in the debate, said Cameron, "I care far too much. This is personal. My name goes back to the West Highlands and I am as proud of my Scottish heritage as I am of my English heritage."
PM invoked the spirit of the Great Britain Olympic team, which won 65 medals in 2012, in a speech at the Olympic Park.
He said: "For me, the best thing about the Olympics wasn't the winning. It was the red, the white, the blue.
"It was patriotism that came out of the shadows and into the sun, everyone cheering as one for Team GB."
What are your thoughts on this? (specify where in the UK you're from)
Nobody would benefit from Scottish independence. I'm from the North East of England but my family on my Dad's side is Scottish and I can't even imagine what it'll be like if Scotland becomes an independent country altogether.
They cant do any worse than we're doing now. Cameron just doesnt want to be known as the PM who broke the union.
I dont think they'll vote for it though, mainly because not a lot of people know much about what'll happen/want to stick with the status quo.
This is essential to Catalonia too, our politicians keep an eye on this whole process, but you Scottish people should be proud to vote, in Catalonia the Spanish government keeps knocking every chance we might have for us to develop our democracy, that's the consequence for having an immature and corrupt state, whether you agree or not you should be able to vote for what you truly want
