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.
"As commander-in-chief, I will never hesitate to defend this nation, but I will only send our troops into harm's way with a clear mission and a sacred commitment to give them the equipment they need in battle and the care and benefits they deserve when they come home," Obama said.
He chided McCain, a staunch advocate of the Iraq war, for saying he would pursue Osama bin Laden to "the Gates of Hell." Obama said McCain's focus on Iraq had let al Qaeda and bin Laden escape.
"John McCain likes to say that he'll follow bin Laden to the Gates of Hell -- but he won't even go to the cave where he lives," he said.
"If John McCain wants to follow George Bush with more tough talk and bad strategy, that is his choice -- but it is not the change American needs."
The speech capped a sunny day of celebration and musical performances by singers like Stevie Wonder and Sheryl Crow under clear skies in the stadium. By the time Obama's speech started, nearly every seat, and the entire football field, was full.
Former Vice President Al Gore, the Nobel Prize and Academy Award winner who lost a disputed election to Bush in 2000, told the crowd things would have been very different if he had won.
"I doubt anyone would argue now that election didn't matter," Gore said, describing Obama as "a clean break from the politics of partisanship and bitter division."
Obama is running even with McCain in most opinion polls, although a Gallup daily tracking poll on Thursday showed him beginning to get an edge from the convention and moving out to a 6-point advantage, up five points.
Obama addressed criticism he has not offered enough specifics along with his sometimes soaring rhetoric, restating an ambitious domestic agenda that includes a tax cut for 95 percent of Americans and an end to dependence on Middle East oil in 10 years.
He said McCain's emphasis on new offshore oil drilling was a stop-gap measure and not a long-term energy solution. He promised to invest $150 billion over the next decade to develop affordable, renewable energy sources.
While Obama's policy proposals were not new, national conventions are often the first time voters pay attention to a presidential race. Opinion polls show many still unfamiliar with Obama and concerned about his readiness for the job.
McCain launched an advertisement on cable television in which he spoke directly to Obama through the camera.
"Too often the achievements of our opponents go unnoticed. So I wanted to stop and say, congratulations," said McCain, who has been scathing in his criticism of Obama.
"How perfect that your nomination would come on this historic day. Tomorrow, we'll be back at it. But tonight, senator, job well done."
The last presidential candidate to accept the nomination in an open-air football stadium was John Kennedy, who spoke to the Democratic convention at the Los Angeles Coliseum before 80,000 supporters in 1960. (David Wiessler/Reuters)