The pope called for an end to the death penalty in the US and across the world.
Francis said that every life is sacred and society can only benefit from rehabilitating those convicted of crimes.
The pope noted that US bishops have renewed their call to abolish capital punishment. That idea is unpopular, however, with many American politicians.
The pontiff did not specifically mention abortion – a particularly contentious issue in Congress at the moment that threatens to force the shutdown of the US government next week.
Still, his remarks referred to the Catholic Church’s opposition to abortion. He urged politicians and all Americans to “protect and defend human life at every stage of its development”
Pope Francis summoned US politicians to defend and preserve the dignity of all Americans, introducing himself as “a son of this great continent” as he became the first pontiff in history to address a joint meeting of Congress.
Entering a House chamber packed with Supreme Court justices, cabinet officials and politicians of both parties, Francis united the often-warring factions before he opened his mouth as the crowd stood to deliver a standing ovation.
The sergeant at arms intoned “Mr Speaker, the pope of the Holy See,” and Francis made his way up the centre aisle in his white robes, moving slowly as politicians applauded enthusiastically, some lowering their heads in bows.
The Argentine pope spoke from the same dais where presidents deliver their State of the Union speeches. Behind him sat vice president Joe Biden and House Speaker John Boehner, the first and second in line to the presidency, both Catholics.
“Each son or daughter of a given country has a mission, a personal and social responsibility,” Francis said in his opening remarks. “Your own responsibility as members of Congress is to enable this country, by your legislative activity, to grow as a nation.”
“Legislative activity is always based on care for the people,” Francis said. “To this you have been invited, called and convened by those who elected you.”
Politicians of all political backgrounds and religious affiliations eagerly welcomed the pope, pledging to pause from the bickering and dysfunction that normally divide them and to listen to the pope. Outside, tens of thousands of spectators gathered on the West Lawn of the Capitol and beyond, and many more were watching on TV around the world.
Security was tight outside the building, with streets around the Capitol blocked off and a heavy police presence that rivalled an inauguration or State of the Union address by the US president.
The scene on the West Lawn of the Capitol was festive but orderly as thousands awaited the pope’s appearance on the House Speaker’s Balcony after his speech to Congress.