Mr Tillerson spoke at a ministerial meeting in Kuwait of the US-led military coalition that has been fighting IS in Iraq and Syria, being held in parallel with a conference on reconstruction in Iraq.
The jihadist group has lost much of the territory it once controlled when it seized large swathes of Syria and neighbouring Iraq in 2014.
"The end of major combat operations does not mean we have achieved the enduring defeat of ISIS," Mr Tillerson said, using another acronym for IS.
"ISIS remains a serious threat to the stability of the region, our homelands and other parts of the globe," he said.
Iraq declared victory over IS in December, but the extremist group still has a presence in Syria, where the US-led coalition has backed a Kurdish-Arab alliance fighting the jihadists.
And Iraqi government forces backed by a US-led coalition last week staged a major operation against "IS remnants" in the northeast.
The US-backed campaign against IS in Syria has been complicated since Turkey-backed Arab militia last month began an offensive against Kurdish forces in the northwestern region of Afrin.
The Turkish operation "has detracted from our fight to defeat ISIS in eastern Syria", Mr Tillerson said of ongoing offensives by US-backed Kurdish militia to clear remaining pockets of extremists.
"Forces have diverted from there to Afrin," he said.
The Kurdish People's Protection Units (YPG) have been a key component of the US-backed alliance fighting IS, but Washington's NATO ally Turkey says they are a "terrorist" offshoot of the outlawed Kurdistan Workers' Party (PKK).
"We remain concerned over recent events in northwest Syria and call on all parties to remain focused on defeating ISIS," Tillerson said.
"We will continue to be completely transparent with Turkey about our efforts in Syria to defeat ISIS," he added, giving a nod to Turkey's right to "counterterrorism efforts" on its border.
Mr Tillerson said the United States would nonetheless maintain an "ISIS-focused military presence in Syria" and "continue to train local security forces" -- a reference to Washington's contentious Kurdish allies.
He said IS had the capacity to re-emerge in liberated territories of Iraq and Syria or elsewhere in the world.
"Every one of us must continue to adapt and strengthen our coalition to counter ISIS' own network of foreign fighters, financing and propaganda.
Iraq seeks support
War-battered Iraq sought Tuesday to attract international investors to rebuild the country at a parallel reconstruction conference in Kuwait, offering hundreds of projects and touting extensive legal guarantees.
"Iraq is open for investors," declared Sami al-Araji, chairman of Iraq's National Investment Commission, on the second day of the conference.
Baghdad says it needs nearly $90 billion to rebuild devastated homes, schools, hospitals and economic infrastructure after three years of war against IS.
It is a tall order, given scepticism about the government's record on corruption.
Iraq in 2016 came 11th from the bottom on Transparency International's Corruption Perceptions Index.
Araji said that Iraq, which has been either at war or under international sanctions since 1980, is offering projects in almost every field of its economy, from oil to agriculture.
World Bank officials joined Iraqi government representatives on Tuesday in Kuwait City to seek pledges from more than 2,000 representatives of international firms.
They talked up legal guarantees available in post-IS Iraq, pointing to an investment law that offers ownership, unlimited cash transfers and tax breaks, among other benefits.
Nizar Nasser Hussein, head of the legal department at the National Investment Commission, said the latest version of the law does not distinguish between foreign and Iraqi investors.
"Foreign investors can establish Iraqi companies," he told AFP, adding that investors would be given lease contracts for 50 years, renewable for a similar period.
Investors will also be exempt from customs duties and income tax for 10-15 years, Hussein said.
Iraq on Monday sentenced a former trade minister to 21 years in jail for corruption, weeks after Interpol handed him over to authorities, a government source said.
He was also sentenced to seven additional years for misconduct.
Araji said investors in Iraq will find "high risks, but high returns".