Defence Secretary James Mattis said Iran has been “put on notice” and that its “continued mischief” in the region will not be tolerated by Donald Trump’s administration.

Mr Mattis called Iran the “single biggest destabilising element” in the Middle East during a rare press conference at the Pentagon along with Chairman of the Joint Chiefs of Staff General Joseph Dunford.

“Iran has been put on notice that the continued mischief they’ve caused around the area, murder they have caused,” and the regime’s support of Syrian President Bashar al Assad, Mr Mattis said.

He warned they are “going to be held to account for it” but did not going into detail about what that entailed.

Mr Mattis has said before he felt Iran posed the largest threat to the US, possibly even more than North Korea though both have been at odds with the US over nuclear weapons for decades.

The Marine general did acknowledge he felt there was “less willingness to be confrontational” on Iran’s part, but added they are still “fundamentally” a destabilising factor in the region.

Mr Mattis also clarified: “Our problem is not with Iran, it’s with the Iranian regime leadership, not the Iranian people. I just want to separate those two as well.”

Iranian President Hassan Rouhani, addressing the country's economic woes exacerbated by US sanctions, said Tehran will defeat any "anti-Iranian" officials within the White House as it recovers from virtual economic isolation.

White House: Trump will not allow Iran to keep making threats against US

One of the sticking points for Mr Mattis and the Trump administration is Iran’s involvement in the Syrian conflict, during which millions have died or fled the country under Mr Assad’s regime.

Mr Mattis asked emphatically, “what are they doing in Syria in the first place?”

He claimed Iran was “propping up” Mr Assad, who has “committed mayhem and murder on his own people”.

Answering his own question, the defence secretary said Iran “has no business” being in the middle of the “civil war”.

He added that the Trump administration is working with Russia, who may have the “traction” and “persuasiveness” to ask Iran to leave, but did not address the issue of Mr Assad asking Tehran to be involved in the first place.

On Syria, Mr Mattis noted the administration’s goal is to move the country “into the Geneva process” in order to establish a government not led by Mr Assad.

President Rouhani summoned to Iran parliament for first time Show all 12 1 /12 President Rouhani summoned to Iran parliament for first time President Rouhani summoned to Iran parliament for first time President Hassan Rouhani speaks at the Iranian Parliament in the capital Tehran AFP/Getty President Rouhani summoned to Iran parliament for first time It was the first time Rouhani had been summoned by parliament in his five years in power EPA President Rouhani summoned to Iran parliament for first time President Hassan Rouhani arrives at the Iranian Parliament in the capital Tehran, on August 28, 2018. - It was the first time Rouhani had been summoned by parliament in his five years in power, with MPs demanding answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April. (Photo by ATTA KENARE / AFP)ATTA KENARE/AFP/Getty Images ATTA KENARE Getty President Rouhani summoned to Iran parliament for first time MPs demanded answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April AFP/Getty President Rouhani summoned to Iran parliament for first time President Hassan Rouhani speaks at the Iranian Parliament in the capital Tehran, on August 28, 2018. - It was the first time Rouhani had been summoned by parliament in his five years in power, with MPs demanding answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April. (Photo by ATTA KENARE / AFP)ATTA KENARE/AFP/Getty Images ATTA KENARE AFP/Getty President Rouhani summoned to Iran parliament for first time Members of the Iranian Parliament gesture as President Hassan Rouhani (not pictured) speaks in the capital Tehran, on August 28, 2018. - It was the first time Rouhani had been summoned by parliament in his five years in power, with MPs demanding answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April. (Photo by ATTA KENARE / AFP)ATTA KENARE/AFP/Getty Images ATTA KENARE AFP/Getty President Rouhani summoned to Iran parliament for first time President Hassan Rouhani speaks at the Iranian Parliament in the capital Tehran, on August 28, 2018. - It was the first time Rouhani had been summoned by parliament in his five years in power, with MPs demanding answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April. (Photo by ATTA KENARE / AFP)ATTA KENARE/AFP/Getty Images ATTA KENARE AFP/Getty President Rouhani summoned to Iran parliament for first time A member of the Iranian Parliament gestures as President Hassan Rouhani (not pictured) speaks in the capital Tehran, on August 28, 2018. - It was the first time Rouhani had been summoned by parliament in his five years in power, with MPs demanding answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April. (Photo by ATTA KENARE / AFP)ATTA KENARE/AFP/Getty Images ATTA KENARE AFP/Getty Images President Rouhani summoned to Iran parliament for first time Members of the Iranian Parliament gesture as President Hassan Rouhani (not pictured) speaks in the capital Tehran, on August 28, 2018. - It was the first time Rouhani had been summoned by parliament in his five years in power, with MPs demanding answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April. (Photo by ATTA KENARE / AFP)ATTA KENARE/AFP/Getty Images ATTA KENARE AFP/Getty President Rouhani summoned to Iran parliament for first time President Hassan Rouhani speaks at the Iranian Parliament in the capital Tehran, on August 28, 2018. - It was the first time Rouhani had been summoned by parliament in his five years in power, with MPs demanding answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April. (Photo by ATTA KENARE / AFP)ATTA KENARE/AFP/Getty Images ATTA KENARE AFP/Getty President Rouhani summoned to Iran parliament for first time A member of the Iranian Parliament gestures as President Hassan Rouhani (not pictured) speaks in the capital Tehran, on August 28, 2018. - It was the first time Rouhani had been summoned by parliament in his five years in power, with MPs demanding answers on unemployment, rising prices and the collapsing value of the rial, which has lost more than half its value since April. (Photo by ATTA KENARE / AFP)ATTA KENARE/AFP/Getty Images ATTA KENARE AFP/Getty Images President Rouhani summoned to Iran parliament for first time epa06977898 Iranian President Hassan Rouhani (R) attends the Parliament session at the Iranian Parliament, in Tehran, Iran, 28 August 2018, to answer lawmakers about the recent local and foreign crisis currently affecting the country. Media reported that President Rouhani is under pressure because of the economic crises and demands for his resignation have increased. Rouhani defended his foreign and economic policy, but the parliament voted that they were not satisfied by the President's response. EPA/ABEDIN TAHERKENAREH ABEDIN TAHERKENAREH EPA

Mr Assad “has denied them [a future] with overt Russian and Iranian support”.

Experts have said the US-Iran relationship has eroded under Mr Trump due to not re-certifying the Iran nuclear deal in May 2018.

Despite the evidence provided by the United Nations on Tehran’s compliance with the deal, Mr Trump said it was too lenient on Iran and has maintained the idea that the country has violated portions of it.

Not re-certifying the 2015 deal and abandoning it meant opening the door for harsher economic sanctions to be placed on the country, the mitigation of which was a key inducement for Iran to comply with the historic deal which sought to stymie the development of its nuclear weapons development programme.

In a lengthy Facebook post, Barack Obama hit out at his successor for the decision to leave one of the key foreign policy accomplishments of his administration, calling it a “serious mistake”.

“There are few issues more important to the security of the US than the potential spread of nuclear weapons, or the potential for even more destructive war in the Middle East. That’s why the US negotiated the Joint Comprehensive Plan of Action (JCPOA) in the first place,” the former president had written.