The head of the world's 1.2 billion Catholics also made another impassioned plea for new immigrants from Latin America to be accepted in the United States, and encouraged them not to be discouraged as they build a new life.
The 78-year-old Argentine pontiff landed in the City of Brotherly Love after a short flight from New York, where he spent a whirlwind 36 hours that included an emotional visit to Ground Zero and mass at Madison Square Garden.
Francis is wrapping up a historic visit to Cuba and the United States this weekend in Philadelphia, with a packed schedule including two appearances at the Festival of Families, an international Catholic gathering.
The city is under a security lockdown, with traffic banned downtown for the entire weekend and thousands of National Guardsmen in the streets to corral throngs of faithful hoping to see the pontiff.
At Independence Hall, where the Declaration of Independence and the US Constitution were debated and signed, Francis told a crowd of tens of thousands that religious freedom must be protected - and be used for the greater good.
"It is a fundamental right which shapes the way we interact socially and personally with our neighbours whose religious views differ from our own," the pope said.
"In a world where various forms of modern tyranny seek to suppress religious freedom... Or to use religion as a pretext for hatred and brutality, it is imperative that the followers of the various religions join their voices in calling for peace, tolerance and respect for the dignity and rights of others."
A debate over the place of religious freedom in American society came to a head this month when a Kentucky county clerk was jailed after refusing to issue marriage licenses to same-sex couples, saying it violated her religious beliefs.
The first Latin American pope also touched on another hot-button issue in US politics: how immigrants fit into American society, and how far the US should open its borders to them.
Francis reminded the large contingent of Hispanics in the crowd: "You bring many gifts to your new nation. You should never be ashamed of your traditions," while also urging them to be "responsible citizens."
"Many of you have emigrated to this country at great personal cost, but in the hope of building a new life. Do not be discouraged by whatever challenges and hardships you face," he said, speaking in Spanish.
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