The White House says the two leaders met privately and had a "very productive discussion", adding that more details would be given later.
The meeting took place inside St Peter's Basilica after they had paid their respects to the Pope, according to Italy's Rai TV, rather than at the US embassy as expected.
This is the first time they have met since that tempestuous meeting in the Oval Office at the end of February, when Zelensky was accused of not saying thank you for US aid to Ukraine.
Only this week, Trump said Zelensky had "no cards to play" in a peace deal with Russia.