His election planning in key primary states such as Wisconsin and West Virginia helped to defuse the anxiety of party heavyweights about Kennedy's Catholicism.

In 1960, he was appointed by President-elect Kennedy to recruit staff for his administration and subsequently took on the job 1961 as the special assistant to the president for congressional relations and personnel.

As DNC chair he established a control structure for communications with state delegates and "dignitaries" which exists to this day; an achievement which cemented his role as perennial party leadership candidate.

After the president was declared dead, O'Brien accompanied the coffin and Jackie Kennedy back to Air Force One at Love Field in Dallas.

After RFK was assassinated, Vice President Hubert Humphrey hired O'Brien to serve as his national presidential campaign director.

He lobbied successfully during President Kennedy's first year for the expansion of the U.S. House of Representatives Standing Committee on rules to ensure a liberal and moderate majority.

Appointed commissioner in 1975, O'Brien oversaw the ABA–NBA merger and negotiated a broadcast agreement with CBS Television while seeing game attendance significantly increase.

In response to public relations issues after the merger, O'Brien pushed for an anti-drug agreement with the NBA Players Association to improve the league's image.

And, although the merger and expansion had solidified the NBA brand and games were broadcast live on weekend days, it still did not have the TV exposure of other pro sports.

O'Brien died of cancer after surgery in Manhattan, New York, on September 28, 1990, at the age of 73, and was interred in St. Michaels Cemetery in Springfield, Massachusetts.