Mr Zarif played an important role in striking a 2015 nuclear deal known as the Joint Comprehensive Plan of Action between Iran and six world powers including the US during the Barack Obama administration. But he came under attack by anti-Western hardliners in the Islamic Republic when Donald Trump pulled the US out of the agreement last May and reimposed sanctions lifted as part of the deal.
Announcing his resignation on his Instagram page Mr Zarif said: “I am apologising you for all the shortcomings in the past years during my time as foreign minister.
“I thank the Iranian nation and officials.”
Iran’s semi-official Tasnim news agency said “some sources have confirmed Zarif’s resignation” but it was not clear whether President Hassan Rouhani would accept it.
Mr Zarif, viewed as a moderate in a government of hardliners, leaves office after being dragged into a powers struggle with conservative ministers who he enraged by declaring “money laundering is a reality”.
Mr Zarif also accused people “with vested interests” of standing in the way of the country falling into line with worldwide standards.
He said: “Those who embark on thousands of billions of rials of money laundering have surely enough financial might to spend tens and hundreds of billions on propaganda.”
Critics who are opposed to the nuclear agreement in the first place seized on his comments as an attempt to make political gains ahead of elections in 2020 and 2021.
Despite his reputation as a moderate, Mr Zarif has been a fierce critic of Western governments and claimed the behaviour of Israel and the US had increased the chance of war in the Middle East when he spoke at the Munich Security Conference earlier this month.
Accusing Israel of violating international law after bombing campaigns in Syria, Mr Zarif also criticised European powers for not calling out Israel and the US for their actions in the region.
He told the conference: “Certainly, some people are looking for war – Israel.”
He has also launched regular broadsides against the Trump administration for its use of sanctions against the Iranian regime.