Obama, the first black White House nominee of a major U.S. party, linked McCain directly to President George W. Bush and said their failed Republican policies were responsible for a faltering U.S. economy and a decline in U.S. global standing.
"We are here because we love this country too much to let the next four years look just like the last eight," Obama told a flag-waving crowd of about 75,000 supporters in Denver's open-air football stadium as he accepted the nomination on the last night of the Democratic convention.
"On Nov. 4th, we must stand up and say: 'Eight is enough,'" Obama said.
Obama delivered the biggest speech in a career filled with big speeches on the 45th anniversary of Martin Luther King's "I Have a Dream" speech -- a landmark in the U.S. civil rights movement.
The speech kicked off a two-month sprint to the Nov. 4 general election against McCain, who tried to steal the limelight with word that he had chosen his running mate and will appear with the choice on Friday in Ohio.
Obama said McCain, an Arizona senator, was out of touch with the day-to-day concerns of Americans and had been "anything but independent" on key issues like the economy, health care and education.
"Now, I don't believe that Senator McCain doesn't care what's going on in the lives of Americans. I just think he doesn't know," said Obama, who had been urged by some Democrats to take a tougher line against McCain.
"Senator McCain likes to talk about judgment, but really, what does it say about your judgment when you think George Bush was right more than 90 percent of the time?" Obama asked, citing McCain's voting record in the Senate.
"I don't know about you, but I'm not ready to take a 10 percent chance on change," he said.
The televised acceptance speech by Obama, who was formally nominated on Wednesday, gave the first-term Illinois senator his biggest national audience until he meets McCain in late September in the first of three face-to-face debates.
The speech included some of the most direct attacks on McCain by Obama since the general election started. Obama, whose patriotism has been the subject of Internet attacks, said the candidates should be able to disagree without attacking each other's character.
"I've got news for you, John McCain. We all put our country first," Obama said.
Obama, an early opponent of the Iraq war, promised to "end this war in Iraq responsibly" but said he would finish the fight against al Qaeda in Afghanistan and would be willing to use U.S. military power when necessary.