The US says the Islamic State (IS) group has committed genocide against Yazidis, Christians and Shia Muslims.
US Secretary of State John Kerry said IS was "genocidal by self-proclamation, by ideology and by actions".
He did not say whether his declaration would lead to a change of US policy in the Middle East.
But he did call for an independent international investigation and criminal charges for those thought to be responsible for the atrocities.
"Naming these crimes is important," Mr Kerry said, "but what is essential is to stop them."
Mr Kerry also said IS was responsible for crimes against humanity and ethnic cleansing in areas it controls in Syria and Iraq.
He said his conclusions had been based on a wealth of evidence provided by the US state department, intelligence teams and other sources.
They include well-documented accounts of IS attacks on the Yazidi community in Iraq, which led to the deaths of hundreds of men and boys and the abduction of thousands of women.
Tens of thousands of Yazidis became stranded on an exposed mountain, and Mr Kerry said "without our intervention, it is clear those people would have been slaughtered".
He also highlighted the killings of Christians in northern Iraq and Libya, and of Shia Turkmen in Iraq.
"The fact is that Daesh [IS] kills Christians because they are Christians, Yazidis because they are Yazidis, Shia because they are Shia," he said, using an Arabic acronym for the group.
"This is the message it conveys to children under its control. Its entire world view is based on eliminating those who do not subscribe to its perverse ideology."
Mr Kerry admitted that a lack of access to IS areas meant the US did not have a "complete picture" of the atrocities that had been carried out, and said he was "neither judge, nor prosecutor, nor jury".
But he said he hoped its victims would take comfort in the fact that "the United States recognises and confirms the despicable nature of the crimes committed against them".
How the UN defines genocide
Article II of the 1948 UN Genocide Convention says genocide means any of the following acts committed "with intent to destroy, in whole or in part, a national, ethnical, racial or religious group, as such". They are:
- Killing members of the group.
- Causing serious bodily or mental harm to members of the group.
- Deliberately inflicting on the group conditions of life calculated to bring about its physical destruction in whole or in part.
- Imposing measures intended to prevent births within the group.
- Forcibly transferring children of the group to another group.
It is only the second time the US administration has declared a genocide during a conflict. The previous time was in 2004 when then-Secretary of State Colin Powell used it to describe the killings in Darfur.
Such a declaration is a powerful signal, says the BBC's diplomatic correspondent Jonathan Marcus, and Mr Kerry may hope that it bolsters the fight against the IS and possibly opens the way to action at the UN Security Council.
But in every other sense its practical impact will be limited, our correspondent adds, as the US and its allies are already engaged in a war against IS and the struggle is likely to continue for months and probably years yet.
Mr Kerry had been given a congressional deadline of 17 March to announce whether IS's actions in areas under its control constituted genocide.
Earlier this week, the US House of Representatives voted 393-0 to designate the crimes as genocide.
Some critics have accused the Obama administration of not speaking out forcefully enough about the treatment of minority groups by IS.
What do we know about the groups targeted by IS?
IS regards Yazidis as devil-worshippers who may be killed or enslaved with impunity.
In August 2014, thousands of Yazidis living in the Nineveh plains of north-western Iraq were rounded up by IS militants. Men and boys over the age of 14 were separated from the women and girls and shot.
The women and girls were abducted as "spoils of war" and openly sold or handed over as "gifts" to IS militants. Girls as young as six and nine years old were raped, witnesses told the UN.
Boys under the age of 14 were separated from their mothers, transported elsewhere and forced to convert to Islam. They were subjected to religious and military training.
IS considers Shia Muslims to be irredeemable apostates subject to punishment by death for their veneration of the Prophet Muhammad's family and other beliefs and practices.
In June 2014, IS militants summarily killed up to 1,700 army recruits, most of them Shia, after capturing the Camp Speicher military base outside the northern Iraqi city of Tikrit.
Also that month, IS began a siege of the predominantly Shia Turkmen town of Amirli. Its 13,000 inhabitants, including 10,000 women and children, were shelled on an almost daily basis until the siege of the town was broken almost three months later.
Christians are considered "People of the Book" under Islamic law, a classification that grants them a certain protection in comparison with other religious groups.
But IS says Christians should not be accorded protection because they are part of a "Jewish- and Crusader-led conspiracy" against Islam. It has forced Christians living in territory it captures to choose between conversion, payment of a protection tax known as jizyah, or death.
In February 2015, IS released a video showing the beheading on a beach in Libya of 21 Egyptian Coptic Christian migrant workers who had been kidnapped in the city of Sirte.