Samantha Power, an unpaid foreign policy adviser and Harvard professor, announced her resignation in a statement provided by the Obama campaign in which she expressed "deep regret."
"Last Monday, I made inexcusable remarks that are at marked variance from my oft-stated admiration for Senator Clinton and from the spirit, tenor and purpose of the Obama campaign," she said. "And I extend my deepest apologies to Senator Clinton, Senator Obama and the remarkable team I have worked with over these long 14 months."
Power's interview Monday was published Friday in a Scottish newspaper, even though she tried to keep it from appearing in print.
"She is a monster, too - that is off the record - she is stooping to anything," The Scotsman quoted her as saying.
As U.S. news media picked up on the remark, Power issued a statement of apology and the campaign said Obama decried the characterization.
In an interview with Irish television station RTE, Power said of the remarks she made about Clinton, "I can't even believe they came out of my mouth."
Shortly before she resigned, the Clinton campaign held a conference call with several of the former first lady's congressional supporters calling for Power to be fired.
"Senator Obama has called for change, and a new kind of politics," said New York Rep. Gregory Meeks. "This is the worst kind of politics."
Clinton spokesman Howard Wolfson noted that those involved in the Clinton campaign had been removed when they spoke of Obama's teenage drug use or helped spread the false rumor that the Illinois senator is a Muslim.
He defended his own comparison of Obama to independent prosecutor Kenneth Starr, saying he'd been responding to "attacks" from the Obama campaign regarding Clinton's tax returns and real estate transactions. That, he said, was a clear reference to Whitewater and so it was appropriate to bring up Starr in that context.
Power also told The Scotsman that Obama's team had been disappointed with Clinton's campaign win in Ohio on Tuesday.
"In Ohio, they are obsessed and Hillary is going to town on it, because she knows Ohio's the only place they can win," Power is quoted as saying.
"You just look at her and think, 'Ergh'," Power is quoted as telling the newspaper. "But if you are poor and she is telling you some story about how Obama is going to take your job away, maybe it will be more effective. The amount of deceit she has put forward is really unattractive."
In a separate interview for Britain's left-leaning New Statesman magazine, published Thursday, Power warned Clinton's campaign against reveling in the trial of Obama donor Antonin "Tony" Rezko, who is facing corruption charges.
"I don't think it's a good idea for the Clintons to get into a competition over who's got the most unsavory donations, you know what I mean?" Power was quoted as telling the magazine.
Power is the author of "A Problem from Hell: America and the Age of Genocide," which won the Pulitzer Prize for general nonfiction in 2003.