Calling the Keystone XL oil pipeline "a distraction" from efforts to combat climate change, Clinton, on the campaign trail in Iowa on Tuesday, said she opposed it.
"I oppose it. I oppose it because I don't think it is in the best interest of what we need to do to combat climate change," Xinhua news agency quoted Clinton as saying.
The pipeline, which would transport oil from Canada to Mexico, has met with fierce opposition from liberals in the Democratic Party who said it would increase the US' reliance on fossil fuels.
Clinton earlier said she wanted to stay out of the debate around the oil pipeline and leave its fate to the Obama administration.
"I was in a unique position as secretary of state at the start of this (review) process, and do not want to interfere with ongoing decision-making that the president and Secretary of State John Kerry have to do in order to make whatever final decisions they need," Clinton said on Tuesday to explain her overdue position.
Clinton said the lengthy review process by the US State Department, initiated by former president George W. Bush, caused her to share her stance with voters.
Clinton's announcement came as controversy around her private e-mail setup during her stint as the US top diplomat threaten to derail her otherwise smooth path to the Democratic nomination.