The congressional body overwhelmingly passed the resolution and also accused the Syrian President Bashar al-Assad of war crimes.
The Syrian government has denied the claims in the past, saying that any fighting it's engaged in has only been against terrorists threatening civilian life.
The conflict in Syria has been raging for five years and this vote means there is now added pressure on President Barack Obama to take further military and diplomatic action against both IS and Syria's president.
Escalated military intervention, and the risk of souring certain diplomatic relations, are thought to be the reasons why the US and also the UK have been reluctant to formally declare the extremist group's actions a genocide.
It is thought more than 250,000 people have been killed by the civil war in Syria so far, while millions more have been made homeless.
The genocide resolution passed 393-0, and the resolution lists Christians among the victims of IS alongside others such as Shia Muslims and Yazidis.
Islamic State's crimes against minorities:
Systematic rape of women
Mass murder
Torture
Kidnapping for ransom
Assassination of church leaders and others
Destruction of churches, monasteries, cemeteries and Christian artefacts
Theft of Christian and other land
The war crimes resolution also passed 392-3, which condemns President Bashar al-Assad's actions in Syria as well as the actions of Syria's Russian and Iranian allies.
It asks President Obama to create an global tribunal to try suspects accused of committing war crimes in Syria.
Congress has given President Obama until Thursday to make a declaration on whether IS is committing genocide or not.
It is unclear whether the White House will do so.
Lord David Alton, a Christian cross-bench peer, has been campaigning for the British government to officially declare the group's campaign a genocide.
He told Premier's News Hour: "I'm delighted that the House of Representatives in America has done this, but of course the European Parliament and the Parliamentary Assembly of the Council of Europe have also passed similar resolutions which just leaves me feeling at the minimum embarrassed and at the maximum pretty angry that the United Kingdom has not done the same.
"We've got to show what makes a country like our own different from organisations like Isis - that we are a country, a society, that believes in the upholding of law."
"This country has a moral obligation to speak out on behalf of those who have no voice."
Listen to Premier's Hannah Tooley speaking to Lord David Alton on the News Hour: