Barack Obama and John Kerry have said ISIS, which is carrying out a lightning offensive in Iraq, could grow in power, destabilise the region and pose a threat to the US.
The American president spoke hours after the Islamist militants made dramatic gains by capturing four towns in western Iraq on Sunday.
Haditha, Anah, Rawa and Rotba - along with a number of villages - were taken as the Islamic State in Iraq and Syria (ISIS) swept east from the Syrian border, where it captured a border crossing on Saturday, in its latest offensive.
The group was also reported to have seized two more border crossings - the Turaibil crossing with Jordan and the al Walid crossing with Syria.
Secretary of State Mr Kerry has arrived in Baghdad on an unannounced visit for talks with Iraq's embattled Prime Minister Nouri al Maliki.
"We're going to have to be vigilant generally," Mr Obama said.
"Right now the problem with ISIS is the fact that they're destabilising the country. That could spill over into some of our allies like Jordan."
Sky's Sam Kiley says Iraqi forces 'folded-up without a fight'
But he said that was just one of an array of threats the US must guard against, citing the group Boko Haram in north Africa and al Qaeda groups in Yemen.
"What we can't do is think that we're just going to play whack-a-mole and send US troops occupying various countries wherever these organisations pop up," Mr Obama said on CBS Face The Nation.
"We're going to have to have a more focused, more targeted strategy and we're going to have to partner and train local law enforcement and military to do their jobs as well."
Secretary of State John Kerry, on a diplomatic tour of the Middle East and Europe, said: "ISIL is a threat to all of the countries in the region and no country is safe from that kind of spread of terror."
John Kerry warned of the 'spread of terror' while speaking in Cairo
Western countries, including Britain, have concerns about the possibility of young men who have joined the insurgency in Iraq or Syria later launching terror attacks at home.
The mother of Reyaad Khan, one of two Britons to appear in an ISIS recruitment film posted online, has made an emotional appeal on Sky News for her son to return home to Cardiff.
Speaking from Baghdad, Sky's Foreign Affairs Editor Sam Kiley said the militants' rapid grab of power "is very significant as it appears the Iraqi army has folded-up without a fight.
"These are major strategic prizes, not necessarily big towns but all of them on the main route to Syria and on the Euphrates river."
Satellite image of Iraqi forces bombing a suspected ISIS target
He added: "The international community is very fearful that if this landscape of ungoverned space becomes established as an Islamist heartland it will attract jihadis from all over the world."
Kiley said the big prize appears to be Haditha, which contains an important power-generating plant for Baghdad.
Dozens of Iraqi tanks, armoured vehicles and special forces troops were being sent to Haditha in an attempt to regain control and protect a dam across the Euphrates, according to Sky sources.
ISIS had already taken control of the cities of Fallujah and Ramadi in predominantly Sunni Anbar province before it seized Iraq's second city Mosul, and Baiji, home to the country's largest oil refinery, in an aggressive offensive in the north.
Cabinet minister Iain Duncan Smith has said the UK could provide logistical support if the US were to begin its own bombing raids.
Young Iraqis have been flocking to recruitment centres at the weekend to join the counter-offensive against ISIS. According to official records, some two million young men have volunteered in the past seven days.