The pontiff's plane touched down at the Philadelphia airport after takeoff from New York, bringing him to a city of blocked-off streets, sidewalks lined with portable potties, and checkpoints manned by police, National Guardsmen and border agents.
After speeches to Congress and the United Nations earlier this week aimed at spurring world leaders toward bold action on immigration and the environment, he is expected to focus more heavily on ordinary Catholics during his two days in Philadelphia.
Francis rode by motorcade to the downtown Cathedral Basilica of Sts. Peter and Paul and celebrated a Mass for about 1,600 people. In his homily, he said the future of the Catholic Church in the U.S. requires a much more active role for lay Catholics, especially women.
"It means valuing the immense contribution which women, lay and religious, have made and continue to make to the life of our communities," he said.
Francis has repeatedly said women should have a greater role in church leadership, though he has rejected the idea of ordaining women.
His praise of nuns marked his second such public expression of gratitude in the U.S. after the Vatican under his leadership ended a crackdown on the main umbrella group of American sisters. Nuns in the cathedral appreciated the gesture.
"We have felt very strong support from him," said Sister Catherine Darcy of Merion, Pennsylvania, one of about 50 members of the Sisters of Mercy of the Americas at the Mass. "We feel he recognizes the contribution that religious (women) make to the church throughout the world."
Also in attendance was the former Archbishop of Philadelphia, Cardinal Justin Rigali, who retired in 2011 amid a scandal over clergy sex abuse.
Rigali retired to the Diocese of Knoxville, Tennessee, months after a grand jury accused the Philadelphia archdiocese of sheltering more than three dozen credibly accused priests and lying about it to victims and others.
After Mass, the pope stopped to bless children in wheelchairs before leaving the cathedral in downtown Philadelphia.
Francis walked through a chapel adjacent to the main room in the cathedral on Saturday to greet ill and disabled parishioners, along with other visitors. He blessed the children and gave them a kiss on the head.