The delegation leaving Sunday includes Mayor Michael Nutter and Archbishop Charles Chaput of the Archdiocese of Philadelphia.
They will be in Rome until March 27 to work with Vatican officials on the eighth World Meeting of Families.
City officials say the September 2015 event could attract more than 1 million people from around the world and be the largest gathering in Philadelphia history.
"I think just being in his presence and understanding the significance of his holiness will have a significant effect on all of us," said Mayor Michael Nutter. "I really don't know what it is going to be like, but I am certainly looking forward to it. It will be an incredible experience, I am sure of that."
The Vatican has not confirmed a papal visit to the U.S., but other popes have attended past world family meetings, and family issues are a top priority for Pope Francis.
Action News will join the Mayor and the rest of the delegation next week.
Brian Taff will be reporting from Rome beginning Monday on Action News.
