He died of septic shock "due to unspecified natural causes," a family spokesman said. Ali died at 9:10 p.m., spending the last hour of his life surrounded by his family. He was initially hospitalized in the Phoenix area on Monday.
His funeral is scheduled for 2 p.m. Friday at the KFC Yum! Center in Louisville, Kentucky.
The spokesman said Ali was a citizen of the world and he wanted people of all walks of life to be able to attend. The funeral will be translated and streamed on the internet.
Eulogies will be given by former President Bill Clinton, Billy Crystal and Bryant Gumbel.
Goodbye my friend. You were Great in so many ways. https://t.co/4rY68GF8mB— Bill Clinton (@billclinton) June 4, 2016
One of the greatest fighters in the history of boxing, Ali became the heavyweight champion at age 22. The 1960s were his glory days, but also a controversial period of his life. After refusing to fight in the Vietnam War, he faced a three-and-a-half year exile from championship fights until the U.S. Supreme Court overturned his conviction on a technicality. His undefeated professional record came to an end in 1971 when he lost to Joe Frazier, but would get revenge in the famous "Thrilla in Manila" rematch.
Ali retired in 1981 after losing to Trevor Berbick in his 61st career bout.
Soon thereafter, Ali -- who doctors said had begun showing signs of sluggishness and neurological damage in the 1970s -- began receiving treatment for Parkinson's disease.
Ali, the G-O-A-T. A giant, an inspiration, a man of peace, a warrior for the cure. Thank you. pic.twitter.com/MCLyJhLC0X— Michael J. Fox (@realmikefox) June 4, 2016
Ali, who called himself "The Greatest," was married four times and had nine children, including daughter Laila, who also became a professional boxer. Ali and his fourth wife, Yolanda "Lonnie" Williams, had been married since 1986.
President Barack Obama and First Lady Michelle Obama released a statement on Ali's death, saying in part, "Like everyone else on the planet, Michelle and I mourn his passing. But we're also grateful to God for how fortunate we are to have known him, if just for a while; for how fortunate we all are that The Greatest chose to grace our time. ... Muhammad Ali shook up the world. And the world is better for it. We are all better for it. Michelle and I send our deepest condolences to his family, and we pray that the greatest fighter of them all finally rests in peace."
Click here to read the full statement from the Obamas on the death of Muhammad Ali
He shook up the world, and the world's better for it. Rest in peace, Champ. pic.twitter.com/z1yM3sSLH3— President Obama (@POTUS) June 4, 2016
Ali's hometown was Louisville, Ky., but Ali briefly lived in Chicago's South Side, including during his exile from boxing. He frequently returned to Chicago, where many of his children lived, and then moved to Michigan in the 1970s.
He first came to Chicago in 1959 to play in the Golden Gloves Championship. But it wasn't until 1964 that he made Chicago his home. Inspired by Elijah Mohammed, he became a Muslim, and changed his name to Muhammad Ali.
"He came here and saw the world as a larger place," said Jonathan Eig, an Ali biographer. "He saw that there were people here who were not the same as him. That black people in Chicago were fighting in a ways he didn't see in his neighborhood in Louisville. "
Ali lived on-and-off in Chicago for more than 12 years, starting in a modest third-floor apartment in the South Shore neighborhood and culminating in a Hyde Park mansion. He married his second wife and raised several of his children in Chicago.
"When he was in Chicago, he was a Chicagoan," Eig said. "He was out on the streets, talking to kids in the neighborhood, hanging out on 79th Street where Nation of Islam had a newspaper office and a bakery. Everybody knew him."
WATCH: MUHAMMAD ALI REMEMBERED IN CHICAGO
On Saturday, people visited a home near 49th and Woodlawn where Ali once lived.
Ali trained at the now-closed Windy City Gym, which was co-owned by Sam Colonna, who now owns a new gym.
"To this day, his name is at least said once or twice a day," said Colonna. "I have a young kid that boxes here and I'll scream out, 'Do the Muhammad Ali jab' and he'll try to mimic Muhammad Ali."
Cleveland Walker was one of Ali's closest friends and said that although the boxer battled Parkinson's disease for 30-years, he never stopped fighting.
"I wish everyone could meet him one-on-one because when you walk away from him he would make you feel like you were his brother or his sister," said Cleveland Walker, a close friend of Ali.
Ali - a brash, big talking fighter - was committed to helping people and made a strong impression on sports reporter Sonny Means during a Golden Gloves competition in the 1950s. Ali paid for the boxing gear Means couldn't afford.
"And we called him the Louisville Lip," said Means, who lives in the south suburbs. "Ali was the type of guy who wouldn't take a back step to anyone."
The Rev. Jesse Jackson dedicated his weekly Rainbow Push broadcast to Ali. He called the heavyweight champion "one of the greatest heroes of all time," saying in a statement: "He sacrificed the heart of his career and money and glory for his religious beliefs about a war he thought unnecessary and unjust. His memory and legacy lingers on until eternity."
"He scarified, the nation benefited," Rev. Jackson continued. "He was a champion in the ring, but, more than that, a hero beyond the ring. When champions win, people carry them off the field on their shoulders. When heroes win, people ride on their shoulders. We rode on Muhammad Ali's shoulders."
Earlier in the day, before news of Ali's death broke, Rev. Jackson was interviewed in the Bay Area where he called Ali a longtime close friend. "My heart is so heavy," Jackson said. "A champion in the ring, a hero outside the ring, a social transformer, an anti-war prophet."
Harvey Mayor Eric J. Kellogg said, "Without the life of Muhammad Ali here on earth, there would be no Michael Jordan, Barack Obama, Beyonce or any other modern day African American icon. We lost a champion for poor people, but God gained the champion of all angels."
"The world has lost not only an American Idol and hero, but a universal icon. He was an instrumental figure in my life as it relates to fighting for the upward mobility of not only Black America, but for every person who have had odds stacked against themselves. We loved him, but God loved him more," said Bishop Larry Trotter of Sweet Holy Spirit Church of Chicago.
WATCH: ABC7 SPORTS REPORTER JIM ROSE REFLECTS ON ALI'S LIFE, LEGACY
Born Cassius Clay on Jan. 17, 1942, Ali first stepped in the ring at age 12 in his hometown of Louisville, Ky., after his bicycle was stolen and a police officer suggested he learn how to box. Ali went on to become one of the most successful athletes and revered public figures in history.
Acclaimed for his quick, dancing style as a fighter, Ali also blended a unique mix of political activism and personal conviction that won him international recognition outside of the ring.
After winning 100 of 108 amateur fights, Ali took home an Olympic gold medal at the 1960 Summer Olympics in Rome. He later allegedly chucked the medal into a river after a waitress at a soda fountain in Louisville refused to serve him because he was black.
Weeks after the Olympics, Ali signed a lucrative contract and won his first pro bout on Oct. 29, 1960, against Tunney Hunsaker. Ali quickly ingratiated himself with the media with his boastful claims and fresh, stylish way of speaking. He told Sports Illustrated in 1961: "Most of them (other boxers) ... can fight almost as good as I can. I'm just saying you never heard of them. And the reason for that is because they cannot throw the jive. Cassius Clay is a boxer who can throw the jive better than anybody."
The brash, underdog Ali promised boxing fans he'd "float like a butterfly, sting like a bee" against Sonny Liston.
At age 22, he stunned the larger Liston, beating the champ in seven rounds in Miami to win his first heavyweight title. In their next match in 1965, Ali floored Liston with a hard, quick blow minutes into the bout and retained his crown when the referee stopped the fight.
PHOTOS: Muhammad Ali through the years
With one Olympic gold medal and a heavyweight belt to his credit, Ali soon began making headlines for his religious and political beliefs.
Inspired by black rights activist Malcolm X, he converted to Islam and changed his name to Muhammad Ali in 1964. When he refused in 1967 to serve in the U.S. Army because of his religious convictions, Ali fended off sharp criticism from a nation that was raw from the dividing forces of the Vietnam War and the civil rights movement. Ali was stripped of his heavyweight title in 1967, fined $10,000 and sentenced to five years in prison for draft evasion. That conviction was overturned by the U.S. Supreme Court in 1971.
There is no death for those who live beyond themselves.— MINISTER FARRAKHAN (@LouisFarrakhan) June 4, 2016
Months later, Ali went head-to-head with Joe Frazier in a legendary 15-round fight. Frazier was unanimously declared the winner of the bruising bout and succeeded Ali as heavyweight champ. Ali said of the grueling fight, "It was like death. Closest thing to dyin' that I know of."
Ali beat Frazier in their next two bouts, including a unanimous 12-round decision in 1974 that set up his heavyweight bout against George Foreman in Zaire (now Congo) 10 months later. Ali won the "Rumble in the Jungle," knocking out Foreman in the eighth round and reclaiming the world heavyweight title. The bout was chronicled in the 1996 documentary "When We Were Kings."
The outspoken champ faced Frazier one last time in an Oct. 1, 1975, bout dubbed "The Thrilla in Manila." Ali defended his title by stopping Frazier after an exhausting 15 rounds in the Philippines. The Ali-Frazier fight trilogy is generally regarded as the finest display of boxing in the history of the sport.
On Feb. 15, 1978, Ali lost his heavyweight title to Leon Spinks, but beat Spinks seven months later to reclaim the crown. He finished his career in 1981 with a record of 56 wins (including 37 by knockout) and five losses.
ALI, THE CIVIL SERVANT
Though gone from the ring, Ali entrenched himself in charitable work and humanitarian causes -- from serving as a United Nations "Messenger of Peace" to supporting hunger and poverty relief. He appeared on the lecture circuit, although the frequency of his appearances lessened when his speech began to slur from his advancing disease.
The father of such memorable quotes as "The man who has no imagination has no wings" provided one of the lasting images of the 1996 Summer Olympics in Atlanta. Before a worldwide audience, he made a surprise appearance at the Games' opening ceremonies, where, his hand shaking from Parkinson's tremors, he took the Olympic torch and lit the stadium cauldron. And at the London Olympics in 2012, he was again a participant in the opening ceremonies.
In 2005, he was awarded the highest U.S. civilian honor, the Presidential Medal of Freedom.
Late last year, Ali hit at Donald Trump following his proposal to temporarily ban Muslims from entering the U.S. "I am a Muslim and there is nothing Islamic about killing innocent people in Paris, San Bernardino, or anywhere else in the world," Ali said in a statement. "True Muslims know that the ruthless violence of so called Islamic Jihadists goes against the very tenets of our religion."
REACTION FROM AROUND THE WORLD
As word of Ali's death spread, statements of love, loss, respect and grief poured in from around the world, from people who knew him or simply admired him.
Sad to hear the passing of Muhammad Ali. He was our hero and truly 'the Greatest'. pic.twitter.com/hIgHhd0KbX— John Dramani Mahama (@JDMahama) June 4, 2016
Ali's fellow fighters - be they former opponents or one of the countless boxers he inspired - as well as others in the sport were also quick to pay tribute.
"We lost a giant today," said Manny Pacquiao. "Boxing benefited from Muhammad Ali's talents but not nearly as much as mankind benefited from his humanity. Our hearts and prayers go out to the Ali family. May God bless them."
"Muhammad Ali is a legend and one of the world's most celebrated athletes, the fighter who ushered in the golden era of boxing and put the sport on the map. He paved the way for professional fighters, including myself, elevating boxing to become a sport watched in millions of households around the world," said Oscar De La Hoya.
In a statement Sugar Ray Leonard said: "I woke up this morning with a tear coming down my cheek, an ache in my chest along with an appreciation of a man, fighter and friend that I truly admired, idolized and loved in Muhammad Ali. My true feelings have not totally surfaced yet because No One beats Muhammad Ali. So to continue his journey I will thank God for bringing this incredible man into my life! RIP Champ"
Until Ali no one said "I'm beautiful" he was royalty, yet common man was his pal. That is beauty. Greatest kind pic.twitter.com/uX7htKHrGc— George Foreman (@GeorgeForeman) June 4, 2016
"He's the most transformative figure of my time, certainly. He did more to change race relations and the views of people than even Martin Luther King. It was a privilege and an honor for me to know him and associate with him," said boxing promoter Bob Arum.
"Without question his legacy is one that he defied the odds because he stood up for what he believed in and when he was put to the test he took personal harm rather than go against his beliefs and what he stood for," said Don King, who promoted both "Rumble in the Jungle" and "Thrilla in Manila."
Former President Bill Clinton, who awarded Ali the Presidential Citizens medal, released a statement mourning his death, saying in part, "Hillary and I are saddened by the passing of Muhammad Ali. From the day he claimed the Olympic gold medal in 1960, boxing fans across the world knew they were seeing a blend of beauty and grace, speed and strength that may never be matched again. We watched him grow from the brash self-confidence of youth and success into a manhood full of religious and political convictions that led him to make tough choices and live with the consequences. Along the way we saw him courageous in the ring, inspiring to the young, compassionate to those in need, and strong and good-humored and bearing the burden of his own health challenges."