In doing so, she shared the stage with former Florida Governor Jeb Bush, who chairs the National Constitution Center.
Bush joined other dignitaries in honoring Clinton's "lifelong career in public service."
"Hillary and I come from different political parties and we disagree about lots of things. But we do agree on the wisdom of the American people - especially those in Iowa and New Hampshire and South Carolina," Bush joked, referring to the three states that have traditionally played pivotal roles in presidential campaigns. Bush joked that Clinton was visiting Des Moines, Iowa, next week. "Now, don't actually wear the medal there, Madam Secretary."
Both families have deep ties to the center, which serves as a national headquarters for civic education and is situated near Independence Hall, where the Declaration of Independence was adopted and the U.S. Constitution was signed. Presidents Bill Clinton and George H.W. Bush received the Liberty Medal in 2006.
Clinton playfully joked that the two ex-presidents are "let's face it, the classic odd couple of American politics." She said the duo "just had one of their annual play dates up in Kennebunkport," at the Bush family compound in Maine.
"Jeb and I are not just renewing an American tradition of bipartisanship. We're keeping up a family tradition as well," Clinton said.
Clinton was feted at an outdoor ceremony on a night filled with politics. She spoke about 90 minutes before President Barack Obama addressed the nation about the crisis in Syria and on the eve of the anniversary of the Sept. 11, 2001, terrorist attacks.
A small group of protesters gathered near the site, some shouting, "Hands off Syria." Others carried signs that read, "Benghazi," a reference to Wednesday's one-year anniversary of the attack on the U.S. diplomatic compound in Benghazi, Libya, that killed four Americans. Some conservatives have criticized Clinton's handling of the incident.
Briefly addressing Syria, Clinton reiterated remarks she made at an unrelated event at the White House on Monday, saying that the "inhuman use of lethal chemical weapons against men women and children ... violates a universal norm at the heart of our global order and it demands a strong response from the international community led by the United States."
"This debate is good for our democracy," Clinton said. "As our founders knew, fervent arguments are the lifeblood of self-government." .
The ceremony included video tributes from former British Prime Minister Tony Blair, groundbreaking tennis star Billie Jean King and Jordan's Queen Rania. They lauded Clinton as a trailblazing figure for women around the globe and a champion of public service.
Others alluded to the possibility of another Clinton presidential campaign.
Amy Gutmann, president of the University of Pennsylvania, said when she was a child it would have been unthinkable that a woman could lead her university, "let alone secretary of state of the United States and something many of us can't wait to celebrate: the first woman president of the United States."
Philadelphia Mayor Michael Nutter, a longtime Clinton supporter, predicted "she will be the first first lady to walk back into the White House in her own right" as president.
Clinton, seated on stage, smiled as she listened to the tributes. She said later she was "overwhelmed" by the tributes and recalled the "patriots who met right here in Philadelphia over in Independence Hall 226 years ago."
"They knew that in a democracy citizens cannot sit on the sidelines, that we have to 'get into the arena,' as Teddy Roosevelt called it, and participate in the debates that shape our country's future," Clinton said.