French Oil company Total announced it will exit Iran on Monday.
The news comes after the US applied pressure on foreign firms doing business with Iran.
"Anyone doing business with Iran will NOT be doing business with the United States," President Donald Trump said on August 7.
Other European countries have also announced their withdrawal from the country, including shipping giant Maersk and car maker Peugeot.
Total, France’s largest energy company, has pulled out of a large Iranian energy project under pressure from the United States.
The Iranian oil minister announced the withdrawal of Total from the country on Monday, RT and DW reported.
"Total has officially left the agreement for the development of phase 11 of South Pars [gas field]," Iran Oil Minister Bijan Namdar Zanganeh said, according to government-run ICANA news agency and RT.
The withdrawal was sparked by a reinstatement of US sanctions which cover foreign firms doing business with the Tehran. President Donald Trump tweeted earlier this month: "Anyone doing business with Iran will NOT be doing business with the United States."
Total said in a statement given to DW: "Total has notified the Iranian authorities of its withdrawal from the contract following the 60-day deadline for obtaining a potential waiver from the US authorities. Despite the backing of the French and European authorities, such a waiver could not have been obtained."
Total had committed to work on the South Pars gas field, which borders Iran and Qatar and holds the largest natural gas reserves in the world. The project is worth $4.8 billion.
Other European firms including Maersk and Peugeot have also recently left Iran, despite pledges from EU officials to shield them from the US sanctions.
In May, EU officials said they would enforce a "blocking statute" which was planned to protect European firms from sanctions.
"As the European Commission, we have the duty to protect European companies. We now need to act, and this is why we are launching the process to activate the 'blocking statute' from 1996," EU Commission President Jean-Claude Juncker said before his July meeting with President Trump.
The US withdrew from the nuclear deal they signed with Iran in 2015. The agreement had lifted crippling sanctions on Iran in return for a commitment from the Islamic Republic to abandon its nuclear enrichment programme. But the US has since reinstated sanctions on Iran.
The EU, China, and Russia condemned the US sanctions and said they would only recognize an agreed mandate form the United Nations.
China is defying the sanctions, continuing its trade with Iran and importing around 767,000 barrels of Iranian oil a day, giving the country a lifeline and keeping China’s needs for oil met, Reuters reported.
The US sanctions came back into force on August 7 on cars, gold, and other metals. A second round is due to take effect on November 4 which will be more severe, targeting oil, shipping, and the Iranian Central Bank.