The cause of death was septic shock from unspecified natural causes, Reuters reported Saturday.
He was the first boxer to win the world heavyweight title three times, retiring in 1981 with a record of 56-5, with 37 knockouts. In 1999, he was named Sportsman of the Century by Sports Illustrated and Sports Personality of the Century by the BBC. Time once referred to him as the "best-known person on the planet."
But he also spent much of his illustrious career shadowed by controversy. As his fame grew, Ali joined the black separatist group Nation of Islam, changing his name from Cassius Clay. He was then forced to sit out several of the prime years of his career for refusing to join the U.S. Army during the Vietnam War.
After his boxing days ended, Ali immersed himself in philanthropy as he dealt with the onset and advance of Parkinson's syndrome.
Born Cassius Clay Jr. on Jan. 17, 1942, in segregated Louisville, Kentucky, Ali was an unlikely candidate for global stardom. At age 12, his bicycle was stolen, and he told a local police officer that he planned to beat up the thief. The officer, Joe Martin, who also coached boxing, advised the young boy to learn how to fight first and took him under his wing.
With his stiff jab and agility, the youngster was a natural. He won more than 100 amateur bouts by most accounts, capturing several Golden Gloves championships. His crowning achievement as an amateur was winning gold at the 1960 Olympics in Rome at 18 years old, when he defeated Poland's Zbigniew Pietrzykowski in the light heavyweight final.
He soon turned professional, backed by a collection of businessmen known as the Louisville Sponsoring Group. He first fought for the world title in 1964 against heavyweight champ Sonny Liston, ushering in an era in which Ali would dominate headlines.
Brash, handsome and outspoken, 22-year-old Ali was the polar opposite of Liston, an old-school brute who was reputedly tied to the mob. Ali taunted Liston, calling him the "big ugly bear." In the pre-bout hype, Ali announced he would "float like a butterfly and sting like a bee," a verse that became etched in pop culture. He also declared himself "the greatest," which became his nickname.
"It's not bragging if you can back it up," Ali said.
During the bout on Feb. 25, 1964 in Miami, he captured the world heavyweight title when Liston failed to answer the bell for the 7th round. It would be the last time Ali would fight as Cassius Clay. He joined the Nation of Islam and renamed himself shortly after the fight, prompting some to denounce him as a radical. (He would leave the group a decade later, converting to the more mainstream Sunni Islam.)
In a rematch on May 25, 1965, Ali knocked Liston out in the first round. He was photographed glowering over his fallen adversary in what's become one of the most iconic images of Ali ever captured.
In 1966, Ali refused induction into the military as the Vietnam War raged, saying he was a conscientious objector protected by his religious beliefs. While critics called him a draft dodger, Ali stood his ground, risking prison time and winnings.
"Why should they ask me to put on a uniform and go 10,000 miles from home and drop bombs and bullets on brown people in Vietnam while so-called Negro people in Louisville are treated like dogs and denied simple human rights?" he said, according to the BBC. "I ain't got no quarrel with them Viet Cong," he famously declared.
The U.S. Department of Justice battled him in court, and in 1967 Ali was convicted of refusing military service. He was suspended by the World Boxing Association and stripped of the WBA heavyweight boxing champion title; other organizations followed suit in denying Ali a license to fight.
In 1970, three and a half years after his suspension, Ali began fighting again when the City of Atlanta Athletic Commission granted him a license. The state of New York soon followed suit after a federal judge ruled Ali's license application should not be denied on the grounds of his conviction because the organization did not deny other athletes for the same reason. The Supreme Court of the United States overturned Ali's conviction on a technicality in 1971.
Despite losing years of his prime, Ali quickly adjusted. Two fights into his comeback, he laced up his gloves for the so-called "Fight of the Century" on March 8, 1971, against reigning champion Joe Frazier. Ali lost in a 15-round decision, but would avenge that defeat with victories over Frazier in 1974 and '75, the latter match known as the "Thrilla in Manila."
But it was a 1974 championship bout in Kinshasa, Zaire, against younger champ George Foreman, that solidified Ali's reputation as a shrewd tactician. Ali adopted what he called a rope-a-dope, covering up at the rope to allow the more powerful Foreman to throw numerous punches without inflicting too much damage. In the eighth round, Ali attacked the fatigued Foreman and won the so-called "Rumble In The Jungle" by knockout.
Ali held the world heavyweight title until being upset by unheralded Leon Spinks in 1978. He regained the title for a third and final time in a rematch against Spinks that same year, but his skills were eroding and he announced his retirement from boxing in 1979. However, he returned the following year at age 38 to fight Larry Holmes, in an attempt to win a fourth world heavyweight boxing championship. Ali lost that fight and his next, against Trevor Berbick in December 1981. He retired permanently after the loss, on a unanimous 10-round decision.
In 1984, at age 42, Ali was diagnosed with Parkinson's syndrome, which shares symptoms with the degenerative neurological condition of the same name. Some believe Ali's condition was brought on in part by the many blows his body had absorbed over the years.
"Maybe my Parkinson's is God's way of reminding me what is important. It slowed me down and caused me to listen rather than talk," he said, according to the BBC. "Actually, people pay more attention to me now because I don't talk as much."
Despite his health concerns, Ali remained an active philanthropist through his post-boxing days, supporting the Special Olympics, Make-A-Wish Foundation, the Muhammad Ali Parkinson Center in Arizona and a museum bearing his name in Louisville.
"Many fans wanted to build a museum to acknowledge my achievements," he said. "I wanted more than a building to house my memorabilia. I wanted a place that would inspire people to be the best that they could be at whatever they chose to do, and to encourage them to be respectful of one another."
A trembling Ali made a surprise appearance at the 1996 centennial Olympic Games in Atlanta, lighting the Olympic Cauldron during the Opening Ceremonies. The touching moment is considered one of the greatest in Olympics history, and also served as one of the few live televised memories of Ali for those too young to have seen him fight. Sixteen years later at the London Games, Ali made another surprise appearance for the Olympic flag presentation.
Ali also worked on numerous humanitarian missions while mingling with world leaders as a U.N. Messenger of Peace, receiving the Presidential Medal of Freedom from then-President George W. Bush in 2005.
Former President Bill Clinton expressed admiration for the champion's craft and determination in a 2012 interview.
“He made it part-theatre, part-dance and all power," Clinton said. "He was unique. And then he risked it all to oppose the Vietnam War. It could have destroyed him. But it didn't because people realized he was prepared to pay the price for his convictions."
Ali saw much less of the spotlight in recent years, but re-emerged from time to time for public appearances.
In 2014, after claims that Ali was in dire health, he opened an Instagram account. He posted vintage photos and even a recent selfie. In December 2014 he appeared in Reno, Nevada, to watch his grandson in a high school football game. Later that month, he was briefly hospitalized with a urinary tract infection. He returned to the hospital for follow-up care on the infection in early 2015.
Ali is survived by his fourth wife, Lonnie. He had nine children: Laila Ali, who became a professional fighter; Rasheda Ali; Maryum Ali; Miya Ali; Hana Ali; Jamillah Ali; Khaliah Ali; Asaad Amin; and Muhammad Ali Jr.
A private funeral will be held Friday in Louisville, with former President Bill Clinton among those giving eulogies.
This article has been updated detail of the cause of death and Ali's funeral.