The 24-hour trip comes just days after Italy's Prime Minister Matteo Renzi became the highest-ranking European leader to visit Tehran since July's nuclear accord.
"This visit is an important step towards building cooperative relations between the EU and Iran," Mogherini said in a statement.
She last visited Iran in July shortly after world powers -- the US, Britain, China, France, Russia and Germany -- agreed to lift damaging sanctions in return for Tehran accepting strict curbs to prevent it acquiring nuclear weapons.
Trade, humanitarian aid, civil nuclear cooperation and human rights will be on the agenda, an EU statement said.
Brussels is also looking to Tehran to help ease Europe's migration crisis as Iran, host to millions of Afghan refugees, is a source of onward flows to the 28-nation bloc.
"Migration is a very important theme for discussion," a senior EU official said.
The official added that Mogherini, who personally helped negotiate the nuclear deal, will also seek to advance diplomatic efforts on Syria and Yemen, two regional conflicts where Iran plays a role.
But the EU wants Iran to do more to fight money laundering and terrorism financing, which are impediments to foreign investment, the official said.
The EU is also interested in future energy imports from Iran in order to break its dependence on Russia.
Industry commissioner Elzbieta Bienkowska, transport commissioner Violeta Bulc and energy commissioner Miguel Arias Canete will be among those travelling with Mogherini.
She will meet Foreign Minister Javad Zarif, parliament speaker Ali Larijani and the secretary of the Supreme National Security Council, Ali Shamkhani, an EU statement said.
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