The resolution was narrowly approved by the House Foreign Affairs Committee.
Turkey, a key US ally, responded by recalling its ambassador in Washington for consultations. It has fiercely opposed the non-binding resolution.
The White House had warned that the vote would harm reconciliation talks between Turkey and Armenia.
The resolution calls on President Barack Obama to ensure that US foreign policy reflects an understanding of the "genocide" and to label the World War I killings as such in his annual statement on the issue.
It was approved by 23 votes to 22 by the committee.Within minutes the Turkish government issued a statement condemning "this resolution which accuses the Turkish nation of a crime it has not committed".
The statement also said the Turkish ambassador was being recalled for consultations.
A Turkish parliamentary delegation had gone to Washington to try to persuade committee members to reject the resolution.
Turkey accepts that atrocities were committed but argues they were part of the war and that there was no systematic attempt to destroy the Christian Armenian people.
The Armenian government welcomed the vote, calling it "an important step towards the prevention of crimes against humanity".
In 2007, a similar resolution passed the committee stage, but was shelved before a House vote after pressure from the George W Bush administration.
During his election campaign Mr Obama promised to brand the mass killings genocide.
"I believe that Turkey values its relationship with the United States at least as much as we value our relations with Turkey," he said.
The Turks, he added, "fundamentally agree that the US-Turkish alliance is simply too important to get side-tracked by a non-binding resolution passed by the House of Representatives".
In October last year, Turkey and Armenia signed a historic accord normalising relations between them after a century of hostility.
Armenia wants Turkey to recognise the killings as an act of genocide, but successive Turkish governments have refused to do so.
Hundreds of thousands of Armenians died in 1915, when they were deported en masse from eastern Anatolia by the Ottoman Empire. They were killed by troops or died from starvation and disease.
Armenians have campaigned for the killings to be recognised internationally as genocide - and more than 20 countries have done so.
While, I may not know a lot about this, I do agree that it was in fact genocide. Having said that...