O’Connell has a doctorate in canon law from The Catholic University of America, where he later served as president from 1998 to 2010. He has served as bishop of Trenton, which covers four counties in central New Jersey, since 2010.

He has suffered from health problems. In December 2014, O’Connell had the lower part of his left leg amputated because of recurring infections caused by diabetes. After physical therapy, he returned in April 2015 to celebrate Mass on Palm Sunday at the Cathedral of St. Mary of the Assumption in Trenton.

In November 2023, he was elected chairman of the U.S. Conference of Catholic Bishops’ Committee on Catholic Education, which provides guidance for Catholic elementary schools, secondary schools, and colleges. 

The committee also, according to the bishops’ conference’s website, “advocates for federal public policies in education that are consistent with Catholic values and that uphold parental rights and responsibilities regarding education.”