Leaders of 27 European Union countries, not including the UK, are meeting in the Italian capital to celebrate 60 years since the Treaty of Rome was signed.
The countries will sign a new declaration to honour the 1957 treaty, which paved the way for the bloc’s foundation.
British Prime Minister Theresa May is not attending the celebrations.
She plans to launch the Brexit process on Wednesday.
Supporters and opponents of the EU are planning marches in Rome.
Security has been tightened across the city following Wednesday’s terrorist attack in London.
Pope Francis welcomed the leaders to the Vatican on the eve of the summit.
In a speech, he said that all bodies risk dying if they do not look ahead, and thus urged the EU to approach the future with renewed vigour.
He also warned against “false forms of security” promised by populists who want to wall themselves off, and instead urged greater solidarity.
The original Treaty of Rome launched the European Economic Community, the EU’s forerunner.
It was signed by six countries: Belgium, France, Italy, Luxembourg, the Netherlands and West Germany.
The US was among those countries that sent congratulatory messages to EU leaders.
“Together we look forward to another 60 years and more of shared security and shared prosperity,” read the White House statement.
President Donald Trump has more often been critical of the union, calling Brexit a “good thing“, and predicting more countries will follow suit.
The tough road ahead – by Damian Grammaticas, Europe correspondent
In a new Declaration of Rome, the 27 countries are reaffirming their shared desire to continue with what is a greatly expanded and deepened union.
But there are huge challenges.
The UK’s looming exit is the Union’s biggest setback ever.
And after a decade of crises and sense of growing threats at home and abroad, European leaders are looking for ways to reinvigorate their project, but struggling to find a united way forward.