It was shortly after winning the title that the 22-year-old, in March 1964, officially changed his name from Cassius Clay.
Ali's title reign was cut short, however, when he was stripped of his belts in 1967 for refusing induction into the U.S. armed forces. The boxer was fiercely opposed to the Vietnam War.
"He walked out of his boxing career and he said, I'm not going to do it," photographer Danny Lyon
remembered. "I'm not going to be the greatest fighter in the world and all these millions of dollars involved, because I have principles. And one of them is I'm not going to go kill some Asians because you guys are asking me to.
For three years, Ali couldn't get a boxing license, and it wasn't until 1971 that his conviction was overturned by the U.S. Supreme Court.
Lyon got to know Ali in 1970, spending three days with him on a freelance assignment for The Sunday Times in London.
"I wasn't particularly interested," Lyon said. "I tended to say no to any assignment; I did very few of them. And I wasn't really a sports nut. And (my wife) said to me -- it's one of the best things she ever said -- 'What, are you crazy?' "
Lyon tagged along with Ali as he trained in Miami Beach, Florida, for his first fight since his conviction. Like Ali, Lyon was opposed to the Vietnam War. He had been a civil rights worker who was once in jail with Martin Luther King Jr. and had roomed with John Lewis.
"The war was a big factor in my life, too, because it just turned me off from American society, which it did a lot of people," Lyon said. "I mean, that's when the hippies where really raging and there were terms about dropping out of society."
Some of Lyon's most famous work came during the 1960s, when he took photos inside the Texas prison system and rode along with outlaw motorcycle riders.
His Ali photos, seen in the gallery above, are a section of the book "The Seventh Dog,"
Lyon's retrospective of a photography career spanning 50 years.
The photos show Ali not only training in Miami Beach, but also mingling with people on the street and around the city.
"There was an amazing kind of humility to this guy," Lyon recalled. "I can't quite explain it."
Ali was known for his cockiness, boasting about being "The Greatest" and often insulting his opponents. But Lyon said Ali was very gracious with everyday people who approached him.
Lyon told a story about when he and Ali were standing on a street corner. A bus was approaching.
"(Ali) says, 'Watch this.' And when the bus stops to let everyone off, he just kind of stands there by himself," Lyon said. "Someone says: 'That's him! That's Ali!' And every single person on that bus comes over to him and wants to shake his hand. In fact, they stopped the bus because they saw him standing there.
"And he shook everybody's hand and he smiled and he was completely sincere. So he was, on the one hand, showing how much people loved him. But I think he loved them back in a very real way. It was very touching."
Lyon said it can be problematic taking photos of celebrities, and it's something he has avoided for most of his career.
"It's basically, all the other people's pictures of them look exactly the same," he said. "And on many pictures of celebrities, the only real interesting thing is the fact that it's Winston Churchill or whoever it is, you know? ...
"But I did like this guy, and I just remember sitting in the car thinking, how can this guy be Muhammad Ali? How can he be so famous and who he is and be so human?"
Lyon hasn't seen Ali in person since they parted ways in 1970, but he said he still admires the boxer and his outspokenness.
"We've never had another Ali," he said. "We've never had someone who really has stood up to the whole establishment and said, 'I'm not playing these games. I'm a real guy and I have real opinions and they're not like yours.'
"Remarkable. A great man. A really, really great man."