Perez assumed the post in a ceremony Tuesday at the Cathedral Basilica of Saints Peter and Paul.
Perez, the former bishop of Cleveland, is the first Hispanic archbishop to lead the five-county archdiocese. He is the 14th Roman Catholic bishop and 10th archbishop of Philadelphia.
He succeeds Archbishop Charles Chaput, who stepped down after turning 75 last year, the traditional retirement age for Catholic bishops.
The Mass of Installation followed a procession of hundreds of cardinals, bishops, priests, deacons and seminarians to the city's cathedral church.
Perez attended the diocesan seminary in Philadelphia in the 1980s and served in a number of Philadelphia parishes before being named as an auxiliary bishop in Rockville Centre, New York, and then bishop of Cleveland in 2017.
A short time before the ceremony, Perez spoke with Action News about coming back to lead the archdiocese where he studied years ago.
"It's coming around full circle. It's amazing. I've been staying here at the cathedral the last couple of days in the room I occupied when I was a deacon stationed at the cathedral, I was ordained in this cathedral a priest. So, it's pretty surreal," he said.
And only Action News was there as younger clergy-members presented gifts to outgoing Archbishop Charles Chaput in a show of gratitude for his leadership and service.
Chaput spoke about his successor in glowing terms saying, "He is certainly going to bring a bunch of new energy to the archdiocese. I am very, very pleased with the holy father's decision to appoint him. So, I'm praying to God with thanksgiving every day for the gifts of Archbishop Nelson Perez," Chaput said.
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We also spoke with members of Archbishop Perez's family who were here for the installation mass.
Christine Sesin says while everyone else sees Archbishop Perez, she still sees him as her loving cousin Nelson who always made time for family.
"As he progressed within the church he always told me how he looks forward to performing my wedding and baptizing our kids and that's exactly what he did," she said.
Meanwhile, Archbishop Perez says he is still amazed at how far his spiritual journey has taken him.
In fact, he says he just recently had that discussion with Pope Francis.
The Archbishop says, "I said to the Holy Father, 'I was made in Cuba, and packaged in Miami, and so here I am you know, and end up in Philadelphia. Spent more than half my life here. God is a God of surprises and this is a surprise."
The Associated Press contributed to this report.