Franklin, 73, originally a gospel singer but best known for her feminist-tinged version of "Respect", will perform for the reform-minded pope in Philadelphia at the September 26 Festival of Families, organisers said.
The 18-time Grammy winner said in a statement that it was "indeed a blessing" to sing for Pope Francis.
The Festival of Families, sponsored by the Roman Catholic Church and put on every three years, also announced that actor Mark Wahlberg would serve as the host of the event.