The US State Department is still studying whether to go ahead with the Keystone XL project.
The Democratic presidential candidate has previously avoided taking a position on the matter.
Now, at a campaign event in Iowa, Hillary Clinton said the pipeline would be a “distraction from the important work we have to do to combat climate change”.
“Therefore, I oppose it,” she told supporters.
Until now, former Secretary of State Hillary Clinton had avoiding giving an opinion on the project, saying she did not want to interfere with the Obama administration’s deliberations.
However, Hillary Clinton’s main rival for the Democratic candidacy, Bernie Sanders, has long opposed the scheme and called on her to make her position clear.
The 1,179-mile pipe was first proposed seven years ago, and would transport oil from the oil sands in Alberta, Canada, to the Gulf of Mexico via Nebraska.
Supporters say the project will create jobs and US increase energy security, while opponents say it will only increase carbon emissions.
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