Rouhani will also visit the Vatican and France on his first overseas trip since the nuclear deal came into force earlier this month, clearing the way for Iran to rebuild its relationship with the West.
The Iranian leader touched down in Rome accompanied by more than 100 ministers, officials and businessmen who are expected to help him clinch deals worth billions in trade and investment, topped by a major order for new Airbus planes.
He smiled broadly for the cameras at Italy's presidential palace before being ushered away for a working lunch with Italian President Sergio Mattarella, the first appointment in a five-day trip.
The fight against the Islamic State group, whose attacks on Paris forced Rouhani to delay a trip originally scheduled for November, and the war in Syria are expected to feature highly in diplomatic contacts during the visit.
Rouhani, 67 and a former academic and diplomat, is seen as a pragmatist who was elected in 2013 on a pledge to end sanctions and improve relations with the West.
He was scheduled to meet Italian Prime Minister Matteo Renzi on Monday evening and will be received by Pope Francis on Tuesday and by French President Francois Hollande on Wednesday.
"We have had friendly relations with Italy and France in the past and we want to continue our good relations with them," Rouhani told reporters before his departure on Monday from Mehrabad Airport.
He also revealed that "important contracts" were in the works with French car makers Peugeot and Renault, adding to a burgeoning list of deals being struck as European companies scramble to get back into a $400-billion (370-billion-euro) economy with the fourth biggest reserves of oil in the world and a consumer market of 80 million people.
National carrier Iran Air said on Sunday it would be buying 114 Airbus planes to modernise an ageing fleet that has struggled to stay in the air as a result of the impact of sanctions.
BILLIONS UP FOR GRABS
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The deal, to be signed in Paris this week, underlines the huge economic stakes involved in Iran's re-opening, particularly for Europe's manufacturing and engineering sectors.
Iran's Transport Minister Abbas Akhoundi said the first Airbuses were earmarked for delivery by March and that Iran was in the market for a total of up to 500 planes.
Peugeot is tipped to forge a car assembly joint venture with Iran Khodro, reviving a partnership which generated Iranian sales of 473,000 units in its last year before the French company pulled out in 2012.
Iranian media reported the deal will involve investment of 500 million euros.
Iran's Central Bank governor said last week the country was counting on the nuclear deal unblocking some $50 billion worth of foreign investment.
Italian companies have been amongst the quickest off the blocks with a major business delegation having visited Tehran in November and some 500 entrepreneurs invited to a forum Rouhani will attend on Tuesday.
Italy was formerly Iran's biggest European trading partner but trade has dwindled to a fifth of its former volume as a result of the sanctions.
Italian media are predicting deals this week worth 17 billion euros, topped by a five-billion-euro contract for pipeline company Saipem.
National carrier Alitalia said Monday it was upgrading its Rome-Tehran service from four a week to a daily flights in anticipation of increased business and tourist travel.
Amid the scramble for slices of the Iranian pie, rights groups fear Tehran's repression of political dissent and extensive use of the death penalty will be forgotten.
Pope Francis is expected to reiterate the Vatican's concerns on both issues, as well as asking Rouhani to help protect Christians in the Middle East.