The Treasury Department said on Wednesday that it was imposing sanctions on Zarif for acting on behalf of Iranian Supreme Leader Ayatollah Ali Khamenei.
"Javad Zarif implements the reckless agenda of Iran's Supreme Leader (Ayatollah Ali Khamenei)," Treasury Secretary Steven Mnuchin said in a statement.
The sanctions freeze any assets Zarif may have in America, the department said.
Zarif tweeted that the US had imposed sanctions on him because it considered him as a threat to its agenda.
The Iranian Foreign Minister brushed off the sanctions on Twitter, saying: "The US' reason for designating me is that I am Iran's 'primary spokesperson around the world'... Is the truth really that painful? It has no effect on me or my family, as I have no property or interests outside of Iran."
"Thank you for considering me such a huge threat to your agenda," he tweeted.
Tensions between the US and Iran heightened since Washington in 2018 withdrew from the 2015 nuclear deal signed between Tehran and world powers. After pulling out from the deal, US President Donald Trump reimposed sanctions on Iran, including measures aimed at slashing its oil exports to zero.
Tehran responded by breaching the limit on its stockpile of low-enriched uranium set under the nuclear deal. It stepped up production of enriched uranium, used to make reactor fuel but also potentially nuclear bombs, in May.
Last week, talks were held in Vienna to try to save the nuclear deal. After meeting representatives from the UK, France, Germany, Russia and China, a senior Iranian official said the atmosphere had been "constructive".
Fears of a direct US-Iranian conflict have risen since May with several suspected attacks on oil tankers in the Gulf, Iran's downing of a US surveillance drone, and a plan for US air raids on Iran in June that Trump called off at the last minute.
In Tehran, Foreign Ministry spokesman Abbas Mousavi reacted angrily at the sanctions targeting Zarif.
"The peak of stupidity and inconsistency of America's leaders is at a point where they don't recognize Dr Zarif as being influential in Iran's policy but with the ultimate ignorance they sanction him! The Americans have a strong fear of the logic of Dr Zarif and his negotiating skills," he wrote on social media.
( With inputs from IANS )