"Our country is less secure and more isolated than it has been at any time in recent history," Biden said in a speech to supporters. "This administration has dug America into a very deep hole around the world at a time our leadership is needed to meet the challenges of the 21st century."
Biden said a central question for the election is which candidate can get the U.S. out of that hole, and he said it is Democrat.
"Nothing is more important than judgment," Biden said in his remarks. "But time and again, on the most critical national security issues of our time, John McCain's judgment was wrong."
The speech offered some of the Obama campaign's strongest criticism to date about McCain's leadership abilities. It was scheduled two days before the first presidential debate, which will focus on foreign policy, and was billed by the campaign as a major speech on foreign policy by the veteran chairman of the Senate Foreign Relations Committee.
Biden listed several examples of what he described as McCain's wrong judgment, such as his contention that the U.S. would be greeted as liberators in Iraq and that the Persian Gulf nation is the central front in the war on terrorism. Biden argued that the president should focus the full U.S. might on al Qaeda in Afghanistan and Pakistan.
"John is more than wrong - he is dangerously wrong. On a question so basic, so fundamental, so critical to our nation's security, we can't afford a commander in chief so divorced from reality and from America's most basic national interests," Biden said.
He spoke at the Cincinnati Museum Center, where President Bush made the case for attacking Iraq.
"Mark my words: If, God forbid, there is another major attack on America, it will not come from Iraq," Biden said. "It will almost certainly come from the Afghanistan-Pakistan border - where the Bush-McCain approach let down our guard and let our enemies off the hook.
"And unlike John McCain - who opposed Barack Obama's call to take out the high-level terrorist targets in Pakistan and called it 'bombing our ally' - we will not tolerate a terrorist sanctuary in Pakistan."
The speech gave Biden a chance to display his policy experience after a recent run of verbal miscues, such as comments to CBS News about Democrat Franklin D. Roosevelt going on television after the stock market crash - although Republican Herbert Hoover was president during 1929 crash, which predated television.
In response, McCain campaign spokesman Ben Porritt said, "Joe Biden, the senator turned salesman, has gone through so many disjointed transformations on Iraq that he no longer represents credible leadership on the issue. ... He has abandoned his criticisms of Senator Obama, and his own firmly held beliefs in order to reflect Barack Obama's record of trying to legislate failure in Iraq and ambition-first style of leadership."