The previously unannounced two-day meeting comes after fruitless talks between Iran and world powers in Vienna earlier this month when no "tangible progress" was made ahead of a July 20 deadline.
The Istanbul meeting was announced on Iranian media, with the ISNA news agency citing a source close to the Islamic republic's nuclear negotiating team.
Zarif left Tehran at around 10 am (0530 GMT) and will head to Algeria tomorrow when his meetings with Ashton end.
No further details of the discussions between Zarif and Ashton were disclosed but several issues reportedly remain.
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These include the scope of Iran's enrichment of uranium, which if further purified could be used to trigger a nuclear explosion, and its unfinished Arak research reactor, whose by-product waste could provide an alternative route to an atomic bomb.
Iranian and Western negotiators said major gaps remained after the talks in Vienna, which failed to spark the start of producing an early draft of a comprehensive agreement.
But all sides have since expressed willingness to continue the talks in the coming months, with the P5+1 seeking to curb Iran's nuclear activities which international monitors suspect could be masking military objectives.
Iran -- which denies ever seeking nuclear weaponry and insists its atomic work is for purely civilian purposes -- wants an end to harsh sanctions choking its economy.
It also wants access to billions of dollars of its foreign assets which were frozen.