The appointment pays homage to the archdiocese and its half-million Catholics.
"It is an honor to have this happen now, while he is still serving in Baltimore," Caine said.
O'Brien is the fourth Baltimore bishop, including his immediate predecessor, William H. Keeler, to be named a cardinal since the archdiocese was founded in 1789. James Gibbons was elevated in 1886, and his hat still hangs from the ceiling of the Basilica of the National Shrine of the Assumption of the Blessed Virgin Mary in Baltimore. Archbishop Lawrence J. Shehan became a cardinal in 1965 and Keeler in 1994. All three remained in their jobs as leaders of the archdiocese.
"Cardinals often come from dioceses that have particular importance in the world church," said Mary Gautier, senior research associate at the Center for Applied Research in the Apostolate at Georgetown University. "Baltimore, as the first [archdiocese] in the U.S., certainly has that."
O'Brien, a New York native, was ordained in 1965 and frequently served as a military chaplain, including a stint in Vietnam with the 173rd Airborne and as archbishop for military services for the 10 years before his arrival in Baltimore. For 18 of his 45 years in the priesthood, he was involved with the military, a duty he welcomed.
"We can all learn from the self-sacrifice of our military leaders and the kids in service," he said.
From the start of tenure here, the city with all its diverse faiths embraced him, he said.
"The city is not as solidly Catholic as it used to be, but there is still great enthusiasm and great respect for the church," he said.
His plan for consolidating the archidocese's schools strengthened the system overall, he said, but forced the closing of 13 schools, including Cardinal Gibbons High.
"That was difficult for me," he said. "In hindsight, I know some are still unforgiving."
O'Brien will be the first in the line of 15 Baltimore bishops that dates to 1789 who will not complete his career in the archdiocese. He will return to Baltimore by the end of the month and expects to remain in the city through the transition in leadership. After that, he said, he plans to be a frequent visitor but will be based in Rome.
His departure will be bittersweet, he said.
"Baltimore has made an indelible impression," he said. "It has been a great experience to lead a diocese as historic as this."