"A man of peace, tenacity and courage has been called home to the Lord," George's successor, Archbishop
He said George died at 10:45 a.m. at his home.
Cupich remembered George as "always choosing the church over his own comfort, and the people over his own needs.
"Let us heed his example and be a little more brave, a little more steadfast and a lot more loving," he added. "May Cardinal Francis George rest in peace."
Monsignor Michael Boland, president of Catholic Charities for the archdiocese, earlier released a statement saying, "Today we mourn the loss of an incredible leader, guiding spirit and loyal friend. Cardinal George had compassion for all. You saw this compassion in his eyes as he visited with the poor and most vulnerable in our communities.
"He was a wonderful mentor to many, including me. He always supported the work of Catholic Charities and it was an incredible blessing to have his leadership help guide us for 17 years. He helped us tackle some of the most difficult issues facing our communities, always with faith and concern for the poorest of the poor. He exemplified our call to feed the hungry and clothe the naked, showing mercy and kindness to all and leading by example.
"Personally, Cardinal George served as an inspiration to me, as I know he did to many in the Archdiocese and around the world. He was unwavering in his support of the mission of Catholic Charities and his deep-rooted faith and love of the Lord shown through in all he did."
George had been on home care since April 3 after being hospitalized late last month for hydration and pain management issues.
As head of the nation's third-largest archdiocese, he shepherded the Chicago church through school closings and the priest sexual abuse scandal, striving to reconcile his support for the clergy with the pain of victims.
He also became a point person between the U.S. and the Vatican on the abuse scandal and matters such as liturgy of the Mass, playing a key role in revisions that brought the English translation closer to the original Latin.
George in November 2014 became the first Chicago archbishop to retire, following his third cancer diagnosis, and was replaced by current Archbishop Blase Cupich.
"He stood apart for his intelligence, his ability to make the church's proposal in a compelling way to contemporary society, his deep faith, personal holiness and courage," said Catholic scholar and papal biographer George Weigel.
"I think he would want to be remembered as a good and faithful priest," Weigel said. "That's all he ever wanted to be."
George received his first cancer diagnosis in 2006 and had surgery to remove his bladder and prostate. He was diagnosed with cancer again about six years later and underwent more surgery.
His most recent diagnosis came in March 2014, when doctors found new cancer cells in his right kidney. He underwent chemotherapy, but the archdiocese announced in late 2014 that he had stopped taking an experimental drug because it had not been effective.
From his childhood on the Northwest Side of Chicago, George embarked on a spiritual career that took him around the globe as a missionary, then brought him back home in 1997 when he was appointed as the eighth archbishop of the Chicago Archdiocese and spiritual leader of its more than 2 million Catholics.
Born Jan. 16, 1937, George went to St. Pascal School in the Portage Park neighborhood, where he knew early on that he wanted to serve the church.
"The first time I thought about being a priest was my first Holy Communion, when I really came to appreciate the nature of that sacrament as much as a 7-year-old could," he said in a church documentary in December 2013 commemorating his 50th anniversary as a priest.
George was 13, not even out of grammar school, when polio struck. When he arrived at Quigley Preparatory Seminary in Chicago on crutches, eager to begin his freshman year, George was told he could not stay and likely never would be ordained. His family enrolled him instead in the now-closed St. Henry Preparatory Seminary, a boarding school in Belleville, Ill., just outside of St. Louis. The school was run by the Missionary Oblates of Mary Immaculate religious order, whose mission is to evangelize the poor and to which he would devote his life.
In 1973 he moved to St. Paul, Minn., to serve as head of the Oblates' Midwestern province, which covers nine states. After just 18 months, at age 37, he was named the worldwide religious order's vicar general, its second in command, and moved to Rome.
As vicar general from 1974 to 1986, George traveled widely, visiting many of the 68 countries where the order's 5,000 members perform their missionary work.
George moved back to the U.S. in 1987 to become the coordinator of the Circle of Fellows at the Cambridge Center for the Study of Faith and Culture in Massachusetts. In 1990 he was installed as bishop of rural Yakima, Wash. Six years later he was promoted to lead the Archdiocese of Portland. He was there only 10 months when
In 2002, at the height of the Catholic Church's sexual abuse scandal, George emerged as a leading figure in negotiations with the Vatican over a zero-tolerance policy. The American bishops' position was that any priest guilty of a single offense of sexual abuse of a minor should be removed from ministry.
As his profile in the Catholic Church rose, the cardinal became more outspoken in articulating the church's stand on national issues, insisting, for example, that Catholic institutions should be exempt from the contraception mandate in President Barack Obama's health care plan.
After the death of Pope John Paul II in 2005, George joined six other American cardinals in Rome for the pontiff’s funeral and the
The new pope's popularity surprised George, who worried that people were developing unrealistic expectations that could lead to further disillusionment with the church.
"He sends out so many signals it gets a bit jumbled at times," George said. "I'm sure he's not confused, himself. It's confusing for a lot of people, including myself at times. For someone who appreciates clarity, I would like to get a few things clear so I can cooperate."