Meanwhile, the president has signed an executive order created to ease a ban on political activity by churches. Along with a bilateral meeting, Trump will attend a Gulf Cooperation Council summit while in Saudi Arabia.
In Israel, Trump will meet with Israeli leaders President Reuven Rivlin and Prime Minister Benjamin Netanyahu, as well as Palestinian Authority President Mahmoud Abbas.
After his trip to Israel, Trump will hop on over to Rome and Vatican City to meet Pope Francis, rounding out what in the end will resemble a tour of the Abrahamic religions.
The three stops will precede Mr Trump's already announced visit to North Atlantic Treaty Organisation and G7 summits in Brussels and Sicily later this month.
"Frankly, Saudi Arabia has not treated us fairly, because we are losing a tremendous amount of money in defending Saudi Arabia", he said.
"The trip is meant to show "'America First' is fully compatible with American leadership in the world", a senior administration official told reporters Thursday.
The weeklong trip will mark the president's first trip overseas and come about six weeks after the US launched Tomahawk missiles against a Syrian air base in the aftermath of a chemical weapons attack in the war-ravaged country.
"We thought that that was a good place to start and look one of the biggest problems that we face in the world today is radical extremism and we have to combat", said the official.
Officials in Washington are reporting that the USA and Saudi Arabia are conducting negotiations for a multi-billion-dollar arms deal.
"Saudi Arabia is the custodian of the two holiest sites in Islam", the president said.
The trip to Saudi Arabia, Israel and the Vatican is a splashy debut for a president who has, until now, largely avoided major trips outside of Washington.
Trump in the public portion of his meeting with Abbas on Wednesday did not mention a key Israeli demand, that Abbas stop payments to families of terrorists killed or jailed by Israel.
As of April, the White House had not approached the Holy See for an audience with the pope during Trump's trip.
The two leaders have previously staked out opposing policy positions, most notably in a heated exchange through the media while Trump was campaigning in February 2016 to become the Republican Party's nominee for the White House.
The meeting will likely be watched closely by many, especially given Trump's penchant for speaking his mind and Francis' habit of making off-the-cuff comments that are often controversial.
In a speech in the Rose Garden at an event on religious liberty, Trump cast his trip as an effort to build cooperation and support between Muslims, Christians and Jews for fighting terrorism.