He received his episcopal consecration on January 6, 1982, from John Paul II himself, with Archbishops Eduardo Somalo and Lucas Neves serving as co-consecrators, in Rome.
He was formally installed as bishop of Phoenix on January 18, 1982, and selected as his episcopal motto "To Build Up the Body of Christ.
In 1990, O'Brien oversaw the development and implementation of a diocesan policy to investigate sexual abuse cases involving priests.
In 2002, Maricopa County prosecutors initiated a grand jury investigation into charges of sexual abuse by Catholic priests in the diocese of Phoenix.
[5] He agreed to cede his authority over diocesan sexual abuse policy in exchange for immunity from indictment for obstruction of justice.
[6] On August 4, 2017, it was announced that a civil lawsuit was filed against O'Brien over allegations that he sexually molested a boy on several occasions at parishes in Phoenix and Goodyear, Arizona, from 1977 to 1982.
[7] On June 14, 2003, O'Brien was driving home from a confirmation ceremony when his vehicle struck a 43-year-old pedestrian named Jim Reed.
[12] In November 2011, the Catholic Community Foundation of Phoenix announced that it was giving O'Brien its faith honoree award.