The 70-year-old former world heavyweight title holder received the Liberty Medal from his daughter, former professional boxer Laila Ali.
The $100,000 (£62,000) award is sponsored by the National Constitution Centre, a non-profit organisation devoted to the US Constitution.
Ali, who once proclaimed himself "the double greatest" but who has been silenced by a long battle with Parkinson's disease, was honoured as an icon of constitutional ideals and the American dream.
The centre described him as "an outspoken fighter for religious and civil rights; a conscientious objector who took his battle to the Supreme Court and won; an ambassador for peace and justice worldwide; and a tireless humanitarian and philanthropist".
Ali, who was diagnosed with Parkinson's in 1984, did not make any remarks after receiving the award. He did manage to wave at the crowds and appeared to examine the medal around his neck.
His wife, Lonnie Ali, spoke to the audience on his behalf.
She said: "On behalf of Muhammad, let me sincerely state how incredibly honoured he is to be here this evening, as the recipient of the Liberty Medal.
"It is, to be honest, overwhelming, especially given the remarkable group of people who have previously been the recipient of the prestigious award.
"It is especially humbling for Muhammad, who has said on many occasions, 'All I did was stand up for what I believe'."
The Olympic gold medalist and boxing legend developed a reputation for being an outspoken fighter for religious and civil rights.
In 1967, Ali refused induction into the US Armed Forces due to his religious beliefs that denounced violence.
He was arrested, fined, stripped of his boxing licence and title and found guilty of draft evasion.
The battle went all the way to the Supreme Court, which reversed the decision in 1971, ruling that his refusal stemmed from constitutionally protected rights. Ali regained his title in 1974 and retired in 1981.
Laila Ali told the audience: "My father loves people and people love my father, and I learnt that at a very young age, as people would always come up to him no matter where we went.
"My father has always lived his life to make this world better for others. He's strong, he's courageous, such a powerful man."
The 2012 Liberty Medal award ceremony was part of the 225th Anniversary of the centre.
An annual award, it was established in 1988 to commemorate the bicentennial of the US Constitution.
