"South Carolina - January 26th is your moment," Winfrey said, referring to the state Democratic primary date during a campaign stop alongside the Illinois senator. "It's your time to seize the opportunity to support a man who, as the Bible says, loves mercy and does justly."
Obama's campaign said more than 29,000 attended the event at the University of South Carolina's football stadium. It had the feel of a rock concert, with bands playing for early arrivals and campaign supporters yelling "Fire it up!" to the crowd.
Winfrey, who also campaigned for Obama on Saturday in Iowa, offered a touch of talk show-like advice during a 17-minute speech. "There are those who say it's not his time, that he should wait his turn. Think about where you'd be in your life if you'd waited when people told you to," she said.
"I'm sick of politics as usual," Winfrey said. "We need Barack Obama."
A recent AP-Pew Research poll has New York Sen. Hillary Rodham Clinton leading in South Carolina with 45 percent of likely Democratic primary voters, followed by Obama's 31 percent. The two candidates break even on the black vote here, and that's where Winfrey's appeal could become a factor - along with her pull among women.
Obama, during his address, criticized the Bush administration and took several veiled swipes at Clinton, though never referenced his rival by name.
"I'm tired of Democrats thinking the only way to look tough on national security is to act like George Bush," he said. "We need a bold Democratic Party that's going to stand for something, not just posture and pose."
He said if he's the party nominee, an opponent won't be able to say he supported going to war in Iraq, which Clinton did.
"It's not good enough to tell the people what you think they want to hear, instead of what they need to hear. That just won't do. Not this time," he said. "We can't spend all our time triangulating and poll-testing our positions because we're worried about what Mitt or Rudy or Fred or the other Republican nominees are going to say about us."
He said voters will need to cast ballots in favor of a candidate - not against an incumbent who is leaving office.
"The name George W. Bush will not be on the ballot," he said, a remark that brought the crowd to its feet for several minutes.
"The name of my cousin Dick Cheney won't be on the ballot," Obama added, a reference to their more than 300-year-old, distant family connection. "That was some embarrassing stuff when that came out."
Obama was accompanied by his wife, Michelle, and said it was his campaign's biggest crowd. "You know you've got a good program when I'm the third-best speaker on the stage," he said.
The event at Williams-Brice Stadium initially was planned for a smaller venue with a capacity of 18,000, but was moved to the stadium after the campaign gave out all of its free tickets two days after distribution began. Organizers said they did not expect to fill the massive arena, however.
About 8,500 people greeted Obama and Winfrey at their last stop in Manchester, N.H., Sunday night, including Gov. John Lynch and the state's two Democratic members of Congress.
After two days of campaigning, Winfrey said she had overcome her initial nervousness.
"I'm beginning to like this," she said. "I'm beginning to like this because I can feel that you are ready for change."
In a slightly different twist on Obama's frequent argument that a long Washington resume doesn't necessarily make for a good president, Winfrey appealed to the parents in the audience.
"You can't be fooled by this experience question because you know it's not the amount of time you spend with your child, it's the quality of that time," she said.
Obama opened his remarks by acknowledging a labor dispute at the arena where the rally was held. He noted that he usually ensures that union workers are involved in his events but that the arena does not employ union workers as stagehands.
"This is a great facility and we should have union workers in here to make sure the stagehands are getting a fair shake," he said, then repeated three times: "I believe in working people."
Kristen Price, 26, who traveled about 120 miles from Bennington, Vt., to Manchester, said Winfrey was the main draw but she ended up as an Obama supporter.
"She played a big role, I'll admit it, but he held his own just fine," Price said.
Price said she had been torn between supporting Obama or Clinton but now considered herself firmly in Obama's camp.
"It was like a religious experience. It was inspiring," she said. "I feel like now America could do anything."