In remarks reported Tuesday by The Tennessean, she said she initially did not want her husband to seek the Republican presidential nomination after a brutal primary struggle in 2000 against George W. Bush.
"The days of Ronald Reagan and Tip O'Neill are what we need to look to: a divided government but a government that needs to agree to disagree," Cindy McCain told reporters after visiting children at a Nashville hospital and prior to the presidential debate. "We're now seeing polarizing factions, people politicizing things that should be about what's best for America. Instead, they're doing what's best for themselves."
The Obama campaign declined to comment.
In 2000, John McCain lost the GOP primary in South Carolina to George W. Bush due in large part to insinuations that he fathered an illegitimate child. The couple adopted one daughter, Bridget, from Mother Teresa's orphanage in Bangladesh.
Her comments came as the McCain campaign's tone has become increasingly harsh.
Nearly every TV ad McCain ran last week was negative, compared to just 34 percent of those by Obama, according to an analysis by the Wisconsin Advertising Project released on Wednesday.
Also on Wednesday, Cindy McCain criticized Obama for voting against a bill to pay for the troops in Iraq.
"The day that Sen. Obama cast a vote not to fund my son when he was serving sent a cold chill through my body, let me tell you," she told a Pennsylvania crowd before introducing the Arizona senator and his running mate Sarah Palin.
In fact, Obama consistently voted for Iraq troop financing except on one occasion. In May 2007, he voted against a troop-funding bill because it did not also specify steps for a withdrawal.
And McCain has not always voted for money for the troops. On one troop-funding bill supported by Obama, McCain missed the vote and encouraged President Bush to veto it, because it did call for withdrawal.