"Wonderful meeting you," said Obama, as the two met outside the Papal Library.
"It is a great honor. I'm a great admirer," he added. "Thank you so much for receiving me."
"I bring greetings from my family," Obama said. "The last time I came here to meet your predecessor I was able to bring my wife and children."
The president has praised Francis before, citing his work to help the poor, as Obama touts his own domestic agenda on income inequality.
In an interview, Obama called the pope a “thoughtful and soulful messenger of peace and justice.”
But the meeting also comes amid tensions between the Obama administration and Catholic leaders in the U.S. over Obamacare's contraception mandate and days after the Supreme Court held oral arguments over a challenge to the measure.
Catholic bishops in the U.S. have been vocal critics of the measure, saying that it infringes on religious liberty.
The meeting comes near the end of a week-long presidential trip to Europe. Obama attended a nuclear summit in the Netherlands and met with European leaders on a trip overshadowed by the crisis in Crimea, which was seized by Russia earlier this month.
Later Thursday, Obama will meet with Italian President Giorgio Napolitano and Prime Minister Matteo Renzi.