The discussions will take place in Geneva on Monday and Tuesday, Iran's foreign ministry said in a surprise statement carried by the official IRNA news agency.
A State Department official confirmed the meeting, noting that the US delegation would be led by deputy secretary William Burns and Wendy Sherman, who is responsible for Iran negotiations.
Iran's foreign ministry also said two days of direct talks with Russia would immediately follow in Rome, in what will be widely interpreted as an all-out diplomatic push to close glaring gaps between Iran and world powers over the future of the Islamic republic's nuclear programme.
"The Iranian vice foreign ministers will hold negotiations with their American counterparts," as well as lead talks with Russian diplomats, the statement said on Saturday.
The unprecedented set of direct bilateral talks come immediately before Iran's next round of political discussions with the P5+1 group — Britain, China, France, Russia, the United States plus Germany — in Vienna, between June 16-20.
Saturday's announcement said Iran was also "working to arrange" other bilateral discussions with members of the P5+1 before the Vienna meeting.
The negotiations with the major powers are aimed at securing a comprehensive agreement on the Islamic republic's disputed nuclear programme ahead of a July 20 deadline.
Several rounds of talks have already been held in Vienna but the latest in mid-May ended with no apparent progress on a deal.
Iran has consistently denied it is seeking nuclear weapons but wants an independent atomic energy programme.
Following the last round in Vienna, Iran urged western powers to resist pressure from third parties not directly involved in negotiations over its nuclear activities, in a clear reference to Israel.
Israel and lawmakers in the US Congress have repeatedly warned against lowering the pressure — in the form of economic sanctions — on Iran.
Major issues between Iran and the P5+1 remain outstanding.
These reportedly 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.
Negotiators aim to nail down an exceedingly complex and lasting deal limiting Iran's atomic activities in exchange for a lifting of sanctions.
Failure could have calamitous consequences, potentially sparking conflict — neither Israel nor the United States rules out military action — and creating a nuclear arms race in the Middle East.