By Todd Leopold, Larry Madowo and Jessie Yeung, CNN

Archbishop Desmond Tutu, the Nobel Peace Prize-winning Anglican cleric whose good humor, inspiring message and conscientious work for civil and human rights made him a revered leader during the struggle to end apartheid in his native South Africa, has died. He was 90.

In a statement confirming his death on Sunday, South African President Cyril Ramaphosa expressed his condolences to Tutu's family and friends, calling him "a patriot without equal."

"A man of extraordinary intellect, integrity and invincibility against the forces of apartheid, he was also tender and vulnerable in his compassion for those who had suffered oppression, injustice and violence under apartheid, and oppressed and downtrodden people around the world," Ramaphosa said.

Tutu had been in ill health for years. In 2013, he underwent tests for a persistent infection, and he was admitted to hospital several times in following years.

For six decades, Tutu -- known affectionately as "the Arch" -- was one of the primary voices in exhorting the South African government to end apartheid, the country's official policy of racial segregation. After apartheid ended in the early '90s and the long-imprisoned Nelson Mandela became president of the country, Tutu was named chair of South Africa's Truth and Reconciliation Commission.

The Nelson Mandela foundation called Tutu's loss "immeasurable."

"He was larger than life, and for so many in South Africa and around the world his life has been a blessing," the foundation said in a statement. "His contributions to struggles against injustice, locally and globally, are matched only by the depth of his thinking about the making of liberatory futures for human societies."

Tutu's civil and human rights work led to prominent honors from around the world. Former US President Barack Obama awarded him the Presidential Medal of Freedom in 2009. Obama called Tutu a "mentor, a friend, and a moral compass" in a statement after his death.

"Archbishop Tutu was grounded in the struggle for liberation and justice in his own country, but also concerned with injustice everywhere. He never lost his impish sense of humor and willingness to find humanity in his adversaries," said Obama.

President Joe Biden also mourned Tutu on Sunday. "His courage and moral clarity helped inspire our commitment to change American policy toward the repressive Apartheid regime in South Africa," the President said in a joint statement with first lady Jill Biden. "His legacy transcends borders and will echo throughout the ages."

In 2012, Tutu was awarded a $1 million grant by the Mo Ibrahim Foundation for "his lifelong commitment to speaking truth to power." The following year, he received the Templeton Prize for his "life-long work in advancing spiritual principles such as love and forgiveness which has helped to liberate people around the world."

Most notably, he received the 1984 Nobel Peace Prize, following in the footsteps of his countryman, Albert Lutuli, who received the prize in 1960.

The Nobel cemented Tutu's status as an instrumental figure in South Africa, a position he gained in the wake of protests against apartheid. Despite anger about the policy within South Africa, as well as widespread global disapproval -- the country was banned from the Olympics from 1964 through 1988 -- the South African government quashed opposition, banning the African National Congress political party and imprisoning its leaders, including Mandela.

It was up to the clergy to take the lead in speaking out, said Rev. Frank Chikane, the former head of the South African Council of Churches and a Tutu colleague.

"We reached the stage where the church was a protector of the people, who was the voice for the people," Chikane told CNN.

The current archbishop of Cape Town and metropolitan of the Anglican Church of Southern Africa, Thabo Makgoba, said that the church will plan Tutu's funeral and memorial services.

"Desmond Tutu's legacy is moral strength, moral courage and clarity," Makgoba said in a statement. "He felt with the people. In public and alone, he cried because he felt people's pain. And he laughed -- no, not just laughed, he cackled with delight when he shared their joy."

In Britain, Prime Minister Boris Johnson and Archbishop of Canterbury Justin Welby issued statements praising Tutu for his sagacity and infectious positivity.

"(He) will be remembered for his spiritual leadership and irrepressible good humor," Johnson said.

Welby called Tutu "a prophet and priest, a man of words and action -- one who embodied the hope and joy that were the foundations of his life."

"Even in our profound sorrow we give thanks for a life so well lived," he said.

The path was rocky

In the 1950s, Tutu had resigned as a teacher in protest of government restrictions on education for Black children, the Bantu Education Act. He was ordained in 1960 and spent the '60s and early '70s alternating between London and South Africa. In 1975 he was appointed dean of St. Mary's Cathedral in Johannesburg and immediately used his new position to make political statements.

"When we were appointed we said ... 'Well, we'll live in Soweto,' " he told the Academy of Achievement, referring to the black townships of Johannesburg. "And so that -- we begin always by making a political statement even without articulating it in words."

It wasn't a plan, though from an early age he'd been inspired by Trevor Huddleston, a priest and early anti-apartheid activist who worked in a Johannesburg slum in the 1950s. By embarking on this path, he inspired thousands of his countrymen -- and more around the world.

"Desmond Tutu had no reason to act as he did other than his profound sense of our shared humanity in working for a world in which justice and the wellbeing of all is an expression of his ethical leadership of compassion," wrote Episcopal priest Robert V. Taylor on CNN in 2011.

Tutu believed he didn't have a choice, even if the path was rocky.

"I really would get mad with God. I would say, 'I mean, how in the name of everything that is good can you allow this or that to happen?' " he told the Academy of Achievement. "But I didn't doubt that ultimately good, right, justice would prevail."

Tumultuous times

Desmond Mpilo Tutu was born October 7, 1931, in Klerksdorp, a town in South Africa's Transvaal province. His father was a teacher and his mother was a domestic worker, and young Tutu had plans to become a doctor, partly thanks to a boyhood bout of tuberculosis, which put him in the hospital for more than a year. He even qualified for medical school, he said.

But his parents couldn't afford the fees, so teaching beckoned.

"The government was giving scholarships for people who wanted to become teachers," he told the Academy of Achievement. "I became a

teacher and I haven't regretted that."

However, he was horrified at the state of Black South African schools, and even more horrified when the Bantu Education Act was passed in 1953 that racially segregated the nation's education system. He resigned in protest. Not long after, the Bishop of Johannesburg agreed to accept him for the priesthood -- Tutu believed it was because he was a Black man with a university education, a rarity in the 1950s -- and took up his new vocation.

The 1960s and 1970s were tumultuous times in South Africa. In March 1960, 69 people were killed in the Sharpeville Massacre, when South African police opened fire on a crowd of protesters. Lutuli, an ANC leader who preached non-violence, was awarded the Nobel Peace Prize later that year -- while banned from leaving the country. (The government finally let him go for a few days to accept his prize.)

Mandela -- then a firebrand leading an armed wing of the ANC -- was arrested, tried and, in 1964, sentenced to life in prison. In the early '70s, the government forced millions of Black people to settle in what were called "homelands."

Tutu spent many of these years in Great Britain, watching from afar, but finally returned for good in 1975, when he was appointed dean of St. Mary's Cathedral in Johannesburg. The next year he was consecrated Bishop of Lesotho. He gained renown for a May 1976 letter he wrote to the prime minister, warning of unrest.

"The mood in the townships was frightening," he told the Academy of Achievement.

A month later Soweto exploded in violence. More than 600 died in the uprising.

A distinctive figure

As the government became increasingly oppressive -- detaining Black people, establishing onerous laws -- Tutu became increasingly outspoken.

"He was one of the most hated people, particularly by White South Africa, because of the stance he took," former Truth and Reconciliation Commission member Alex Boraine told CNN.

Added Chikane, the South African Council of Churches colleague, "His moral authority (was) both his weapon and his shield, enabling him to confront his oppressors with a rare impunity."

South Africa was becoming a pariah country. Demonstrators in the United States protested corporate investment in the nation and Congress backed up the stance with the 1987 Rangel Amendment. The United Nations established a cultural boycott. Popular songs, such as the Special AKA's "Free Nelson Mandela" and Artists United Against Apartheid's "Sun City," deplored the country's politics.

With his scarlet vestments, Tutu cut a distinctive figure as he preached from the bully pulpit -- perhaps never more so than in his Nobel Prize speech in 1984.

After reeling off the prejudices and inequalities of the apartheid system, Tutu summed up his thoughts. "In short," he said, "this land, richly endowed in so many ways, is sadly lacking in justice."

There were more injustices to come: assassinations, allegations of hit squads, bombings. In 1988, two years after being named Archbishop of Cape Town, becoming the first Black man to head the Anglican Church in South Africa, Tutu was arrested while taking an anti-apartheid petition to South Africa's parliament.

But the tide was turning. The next year, Tutu led a 20,000-person march in Cape Town. Also in 1989, a new president, F.W. de Klerk, started easing apartheid laws. Finally, on February 11, 1990, Mandela was released from prison after 27 years. De Klerk died last month.

Four years later, in 1994, Mandela would be elected president. Tutu compared being allowed to vote for the first time to "falling in love" and said -- behind the birth of his first child -- introducing Mandela as the country's new president was the greatest moment of his life.

"I actually said to God, I don't mind if I die now," he told CNN.

Controversial stances

Tutu's work was not done, however. In 1995 Mandela appointed him chair of the Truth and Reconciliation Commission to address the human rights violations of the apartheid years. Tutu broke down at the TRC's first hearing in 1996.

The TRC gave its report to the government in 1998. Tutu established the Desmond Tutu Peace Trust the same year.

He returned to teaching, becoming a visiting professor at Emory University in Atlanta for two years and later lecturing at the Episcopal Divinity School in Cambridge, Massachusetts. He published a handful of books, including "No Future Without Forgiveness" (1999), "God Is Not a Christian" (2011), and a children's book, "Desmond and the Very Mean Word" (2012).

He retired from public service in 2010 but remained unafraid to take controversial positions. He called for a boycott of Israel in 2014  and said that former US President George W. Bush and former UK Prime Minister Tony Blair should be "made to answer" at the International Criminal Court for their actions around the Iraq war.

But he was also distinguished for his sense of humor, embodied in a distinctive, giggle-like laugh.

While visiting "The Daily Show" in 2004, he broke up at Jon Stewart's jokes. And he poked fun at "On Being" interviewer Krista Tippett in 2014, chiding her for not offering him the dried mangos -- his favorite -- she'd brought along.

Despite all the praise and fame, however, he told CNN he didn't feel like a "great man."

"What is a great man?" he said. "I just know that I've had incredible, incredible opportunities. ... When you stand out in a crowd, it is always only because you are being carried on the shoulders of others."

For all of his good works, he added, there may have been another reason he had so many followers.

"They took me only because I have this large nose," he said. "And I have this easy name, Tutu."

Tutu is survived by his wife of more than 60 years, Nomalizo Leah Tutu, with whom he had four children, Trevor, Theresa, Naomi and Mpho.

This story has been updated with additional reaction.