Trump will land at Fiumicino, the capital's largest airport on Tuesday evening before meeting Pope Francis and Italian President Sergio Mattarella the following day.
The president will be accompanied by wife Melania, daughter Ivanka, and Secretary of State Rex Wayne Tillerson, and a large US delegation.
Police chiefs in the capital were set to meet on Monday to finalize details of the security plan, which is made more complex by the Trumps' varying commitments. Melania will visit a children's hospital while her husband carries out his visits, and Ivanka will stay an extra day in the city.
There will be two 'red zones' surrounding the Vatican and Quirinale presidential palace, with limits on road and pedestrian traffic in the area. Several roads are completely closed off to traffic, and tram lines 3 and 19 as well as several bus routes will be diverted. Detailed information about changes to public transport is available from the city's transport site.
Police snipers will be in place on roofs of buildings, and authorities will remove parked cars and wheely bins from the area before Trump's arrival.
Additional police officers will be deployed along the route taken by the president, as well as teams of explosives experts and specially trained dogs.
In addition to the three main security zones - around the Vatican, Quirinale palace, and American ambassador's residence - there will also be increased security around the American embassy and a large 'green zone' in the historic centre, stretching from Piazza Navona to the Roman Forum. Full details of the affected area can be found here.
The president is set to spend around 24 hours in Italy before travelling to Belgium as part of his first foreign tour, which has already taken him to Saudi Arabia and Israel. He will be back in Sicily at the end of the week for a G7 meet in Taormina.
His meeting with Pope Francis comes after months of barbed exchanges through the media. One heated exchange which saw the pontiff appear to question Trump's Christianity and the president angrily respond by saying "if and when the Vatican is attacked by Isis", the pope would "wish and pray" that Trump were president.
The two leaders hold widely different views on areas including climate change and immigration, but Francis vowed last week not to judge the president before hearing him out, while Trump has said he is "very much looking forward" to meeting the pontiff.
Just days before Trump was due to land, a lifesize mural depicting a devil-horned Trump kissing the pope, who wore a halo, appeared in Rome and attracted global headline. The faces on the mural were quickly scrubbed clean by city authorities.
An anti-Trump protest is scheduled for Tuesday evening in the capital's Piazza Bologna.
"As Americans living in Rome we felt upset by the election results but also helpless to make any meaningful change from abroad," one of the organizers, from the group American Expats for Positive Change, said.
"When Donald Trump announced his first overseas trip as president would come to Rome we knew that we had a unique opportunity to express our concerns with his administration."
Organizers had originally hoped to hold the protest outside the American ambassador's residence, where the Trumps are expected to stay, or at the Pantheon where the Women's March was held earlier this year, but the high security in place meant the event had to be held at the square on the north-east outskirts of the city.
Security in the capital is already extremely high, with the terror threat level having been at 2 for several months - the highest possible level in the absence of a direct attack.
Photo: Jim Watson/AFP