This story has been updated.
"As of today, I am not in favor of what I have learned about it," Clinton said in the interview. "I have said from the very beginning that we had to have a trade agreement that would create good American jobs, raise wages and advance our national security. I still believe that's the high bar we have to meet. I've been trying to learn as much as I can about the agreement, but I'm worried."
"I appreciate the hard work that President Obama and his team put into this process and recognize the strides they made," Clinton said in a statement released to reporters traveling with her in Iowa. "But the bar here is very high and, based on what I have seen, I don't believe this agreement has met it."
The trade-preference deal is a key component of the Obama administration's Pacific Rim engagement strategy, which Clinton promoted heavily as secretary of state. While in office, Clinton had called the proposed deal the "gold standard" of modern trade pacts. Long wary of Chinese economic and military expansion, Clinton backed the pact both for its potential trade benefits and for its potential to knit together Southeast Asian and neighboring nations in an economic alliance that, at least initially, would exclude China.
Labor unions and some liberal groups have opposed the deal as a potential job killer.
Clinton's turnabout follows her rejection last month of the Keystone XL oil pipeline still under review by the Obama administration. Both actions put additional pressure on the White House.
In her statement, Clinton said she is "continuing to learn about the details of the new Trans-Pacific Partnership, including looking hard at what’s in there to crack down on currency manipulation, which kills American jobs, and to make sure we’re not putting the interests of drug companies ahead of patients and consumers."
She had said months ago that the currency provision would be a key test for her.
"But based on what I know so far, I can’t support this agreement," she said. ". . . The risks are too high that, despite our best efforts, they will end up doing more harm than good for hard-working American families whose paychecks have barely budged in years."
Clinton's stance aligns her with most of the Democratic Party, including her closest rivals on the 2016 presidential campaign trail. Sen. Bernie Sanders (I-Vt.) and former Maryland governor Martin O'Malley, both running for the Democratic nomination, have opposed the trade deal. Obama won new "fast track" powers in June with support from most of the Republican congressional caucus but only a fraction of Democrats in the face of fierce opposition from organized labor and environmental groups. Just 28 of 188 House Democrats voted in favor of that legislation.
Clinton had been Obama's partner and most effective global advocate for advancing the trade pact while serving as the nation's top diplomat during the president's first term, using the "gold standard" language during a 2012 speech in Australia. Her State Department helped set the direction of the Obama administration's "Asia pivot," a strategic rebalancing of U.S. foreign policy attention away from Europe and the Middle East and toward Asia.
But in the interview with PBS, Clinton cited a lack of protections against nations that have manipulated their currency rates and provisions dealing with market protections for U.S. pharmaceutical companies.
"There are still a lot of unanswered questions," she said.
An administration official said Wednesday that Clinton had given the White House a heads-up ahead of her announcement.
In June, even as she held off announcing a position, Clinton told the crowd at a campaign event that she sided with the House Democrats who had led a rebellion against Obama's trade agenda.
Clinton called on Obama to listen to House Minority Leader Nancy Pelosi (D-Calif.) and the Democratic rank and file in Congress who wanted the trade agreement to include better protections for American workers. If the president didn't, Clinton said then, "there should be no deal."
She also drew a particularly sharp contrast with Obama.
"No president would be a tougher negotiator on behalf of American workers, either with our trading partners or Republicans on Capitol Hill, than I would be," Clinton said.
The controversial pact was already expected to face a rocky reception in Washington. Just hours after Obama hailed the TPP, the largest U.S. trade pact in a generation, as an accord that “reflects America’s values,” the administration had already turned from the negotiating table to selling the agreement on Capitol Hill.
Obama pledged that the pact would open new markets for U.S. goods and services and establish rules of international commerce that give “our workers the fair shot at success they deserve.”
But virtually as soon as the deal was announced, there were signs of the tough fight ahead to win final ratification from Congress next year. Lawmakers from both parties criticized the pact as falling short in crucial areas, raising the prospect that the White House could lose the support of allies who had backed the president’s trade push earlier this year.
On the presidential campaign trail, the anti-trade sentiment has been powerful. Republican front-runner Donald Trump called the TPP "a terrible deal," tweeting that the Obama administration's "incompetence . . . is beyond comprehension."
“I’ll leave the presidential politics to someone else,” U.S. Trade Representative Michael Froman said during a Monday news conference in Atlanta. “Our job is to reach agreement and explain it fully to the American public. Given where we are in the calendar, this really is a 2016 issue for Congress to consider.”
Clinton’s Democratic rivals used her announcement as an opportunity to underscore their long-standing opposition to the pact.
"Wow! That's a reversal," O'Malley said Wednesday. "I was against the Trans-Pacific Partnership months and months ago."
He echoed liberal and labor groups who say the deal would repeat mistakes of the North American Free Trade Agreement of two decades ago.
"We were told in NAFTA all sorts of great promises, and what we got in return were shuttered factories and empty pockets," O'Malley said. "I believe we need to stop stumbling backwards into bad deals."
Sanders said Wednesday he was "delighted" to hear that Clinton had announced her opposition to the trade deal.
After addressing the Congressional Hispanic Caucus Institute, Sanders was asked whether he thought Clinton had credibility on the issue, given that she had helped lay the groundwork for the agreement as secretary of state.
"I'll let the American people determine who has credibility or not. I'm glad that she reached that conclusion," he said. "That's a conclusion I reached from Day One. I believe that the Trans-Pacific Partnership is nothing more than a continuation of disastrous trade policies, which we have experienced for the last 30 or so years, which have led to the loss of millions of decent-paying jobs."
Sanders said he would work hard to defeat the deal in the Senate. Asked whether he thought Clinton would have been against the trade deal if not for his presidential campaign, Sanders winked and said, "I'll let the media speculate on that."
"All I can tell you, whether it is the Keystone pipeline, whether it is TPP, these are issues that I've had a very strong opinion on from Day One," Sanders said. "And I can simply say I am delighted that Secretary Clinton is onboard our position to the TPP. To be very frank with you, it would have been more helpful to have her onboard a few months ago when the fight was 60 votes."
Ed O'Keefe contributed to this report.