More than 500 Britons are believed to have gone to Iraq and Syria and at least half have returned, with some feared to be planning attacks there. One major plot has been foiled.
The warning came as it emerged that a laptop seized from Isis in Syria contained research on how to make a biological bomb and religious justification for using it against civilians.
Tomorrow Cameron will unveil a number of "uncompromising" measures to help tackle British jihadists and fill the "gaps in our armoury".
They will include stopping British fanatics from travelling to or returning from the war zones by making it easier to seize their passports.
He is also expected to tighten controls that can be put on the movement and activities of terror suspects within the UK.
It is the first time in three years that the threat level has stood at severe, just one short of "critical", which would mean an attack is imminent.
Home Secretary Theresa May insisted the move was not a result of any specific plot, but in light of the increasing dangers posed by British fanatics and other foreign fighters in Iraq and Syria.
The change also comes less than a week before a Nato summit in South Wales, which will be the biggest gathering of heads of state in the UK.
The White House said it had consulted with the British Government about the heightened threat level, but there was no plan to raise America's equivalent threat notice.
Cameron said the world had been "shocked and sickened" by the Isis murder of American journalist James Foley, apparently by a British terrorist.
He said he was "absolutely satisfied that Isis has specific threats and will make specific threats to the UK".
Whitehall sources said Isis and other terrorist groups in Iraq and Syria are planning attacks against the UK and other Western countries.
The Prime Minister said: "It was clear evidence that this is not some foreign conflict thousands of miles from home that we can hope to ignore.
"The ambition to create an extremist caliphate in the heart of Iraq and Syria is a threat to our own security here in the UK."
Cameron has been under pressure to join the US in air strikes against the terror group and yesterday would not rule out military action.
Earlier this week Scotland Yard warned that the arrest rate for those suspected of being involved in Syria or Iraq-related terrorism had increased five-fold since last year.
The decision to raise the threat level was taken by the Joint Terrorism Analysis Centre, which operates out of MI5 and is independent of ministers.
May said: "We face a real and serious threat in the UK from international terrorism. I would urge the public to remain vigilant and to report any suspicious activity to the police."
