Bernardin was born in 1928 in Columbia, South Carolina, where there not many Catholics. He was the son of Italian immigrants, with a younger sister Elaine. He was baptized and confirmed at St. Peter's Catholic Church on Assembly Street. His father died when he was six. His mother Maria was a seamstress. At first, Joseph wanted to be a medical doctor, but changed his mind and went to Saint Mary Seminary in Baltimore and the Catholic University of America.
In 1952, Bernardin was ordained a priest in the Diocese of Charleston. In 1959, Pope John XXIII named him Papal Chamberlain. In 1966, in Atlanta, he became the youngest Auxiliary Bishop in America. In 1968, he became General Secretary of the National Conference of Catholic Bishops in Washington, D.C. This was the time of Vatican II, in which the Catholic Church was attempting a more collaborative, modern approach to worship, leadership, and engagement with the world outside the church.
In 1972, Bernardin became Archbishop of Cincinnati, the youngest Archbishop in the country. During this time, he improved relations with Jews and Protestants, visited Poland and Hungary, and became President of the NCCB.
Issues he became active in included abortion, nuclear disarmament, anti-poverty efforts, and social justice. He stood firmly against capital punishment and euthanasia, calling all of these quality-of-life issues part of a "seamless garment of life."
In 1982, Bernardin was chosen by Pope John Paul II as Archbishop of Chicago, the largest diocese in U.S. In Chicago, he saw parish closings and the church's struggle with modernity and progressivism, but he used his skills of compromise to reconcile Catholics to one another and define the role of women in the church.
One of his greatest honors was his elevation by John Paul II in 1983 to the Sacred College of Cardinals.
Bernardin sought common ground on divisive issues with other faiths. He attended the World Parliament of Religions in 1993. He visited Jerusalem and met Palestinian Yasser Arafat.
In 1995, Cardinal Bernardin was diagnosed with pancreatic cancer, and he became the "unofficial chaplain for cancer patients" in Chicago. He faced death with dignity, and, in a sense, taught people how to die. He passed away in 1996.
Bernardin was given the Medal of Freedom by President Clinton. The Loyola Cancer Center was renamed for him. "Bernardin Way" is a street in Columbia near Providence Hospital named for him.