British Airways and Air France have announced that they will stop flying to Iran next month.
Both airlines said that the route was "not commercially viable."
The reintroduction of US sanctions has caused a slump in the value of the Iranian currency, the rial, making it harder for Iranians to travel overseas.
BA restarted the service to Tehran two years ago after a four-year gap. The last flight will be on 22 September, returning the next day.
The airline apologised to travellers planning to travel to Iran and said it was offering refunds for affected customers or a possible rerouting through other airlines.
Air France, which had transferred its connections with Tehran to its low-cost airline Joon, had reduced the frequency of the flights from three to one a week since the beginning of this month. It will stop all flights on 18 September.
KLM said last month that it would also suspend flights from Amsterdam to Iran from September.
The sanctions, prompted partly by Washington's decision in May to abandon the Iran nuclear deal, have prompted many western firms to step back from business in Iran.
Companies such as the French energy giant Total, German insurer Allianz and Danish tanker operator Maersk have said they are preparing to wind down their operations in Iran.