Bad Bunny, whose real name is Benito Antonio Martínez Ocasio, is currently performing a 10-show run in Madrid as part of his Spanish tour.
Leo raised the comparison while discussing what he described as signs of a spiritual awakening among some young people in Spain.
The pope said many young adults appear to be searching for meaning and expressed hope that his visit could help "awaken" something within them.
Despite his remarks, thousands of young Catholics turned out to greet the pope.
An estimated 500,000 people gathered in a Madrid plaza Saturday evening for a prayer vigil, chanting, "This is the youth of the pope!"
Leo later rode through the crowd in his popemobile while a Spanish rendition of the 1970s musical "Godspell" played.
The Chicago-born pope was also asked about reports that the Chicago Bears could soon move out of Illinois.
The team's board of directors voted Thursday to advance a proposed stadium development project in Hammond, Indiana.
"That’s out of my pay (scale)," Leo quipped when asked about the potential relocation.
The Associated Press contributed to this report.