Vatican: Boston archbishop, ally of sex abuse victims, retires
The 80-year-old will be replaced by Richard Henning, the 59-year-old bishop of Providence, to helm the fourth-largest diocese in the United States, the Vatican said in a statement.
It did not give a reason, saying only that Pope Francis had accepted O'Malley's resignation.
In the Catholic Church, bishops who lead a diocese have a traditional retirement age of 75, but the pope has the discretion to ask them to stay on longer.
For now, O'Malley remains head of the Pontifical Commission for the Protection of Minors, a body created by Pope Francis to fight pedophilia by priests that the bishop has led since 2014.
O'Malley's resignation ends a two-decade chapter leading Catholics in the largely Irish and Italian city of Boston, where the global scandal over child sex abuse by clergy erupted in 2002, the year before he arrived.
An ally of Francis, O'Malley is part of the Franciscan mendicant order, Friars Minor Capuchin, and spent his early years as a priest building bridges with the immigrant Hispanic community in the diocese of Washington DC.
Before arriving in Boston, O'Malley served as bishop of Saint Thomas, a diocese covering all the US Virgin Islands, and later of Fall River, Massachusetts, south of Boston.
In Fall River and the diocese of Palm Beach, Florida, he managed the fall-out of scandals involving the sexual abuse of minors by priests.
But it was in Boston where O'Malley came to prominence, managing what was then the highest-profile US clerical sex abuse scandal, later depicted in the Academy Award-winning film, "Spotlight."
Recognized for his rapport with victims and his speed in settling cases, under O'Malley's watch the archdiocese agreed to pay $85 million to settle nearly 550 victim lawsuits.