Lawrence Francis O’Brien was born on July 7, 1917, in Springfield, Massachusetts. O'Brien was introduced to electoral politics at a very early age. His father was a leader of the local Democratic organization and had Lawrence working as campaign worker in Alfred E. Smith’s 1928 presidential campaign.

Soon after World War II, O’Brien ran congressional campaigns for his good friend Foster Furcolo in 1946, 1948, and 1950. In 1948, when Furcolo won the election, O’Brien followed him to Washington, where he served as Furcolo’s administrative assistant. O’Brien retuned to Springfield after the 1950 election and in 1952 served as director of organization in John F. Kennedy’s successful Senate campaign; he also worked on Kennedy’s reelection campaign. Kennedy’s victories were largely attributed to O’Brien’s mobilization of volunteers and his creation of an independent statewide organization. It was Kennedy’s second victory that thrust him into the spotlight as a presidential possibility.

Between senatorial campaigns, O’Brien managed his family's real estate and did public relations work in Springfield. He began laying the foundations for Kennedy’s presidential campaign by touring the country in April 1959. It was O’Brien’s masterminding of victories in key primary states, such as Wisconsin and West Virginia, that convinced many in the party that Kennedy’s Catholicism was not a roadblock.

O’Brien also created an entirely new strategy for the Democratic National Convention which has now become the standard for both parties. He compiled files on each of the voting delegates and the alternatives and, through a complicated communications system, kept in touch the liaison for every delegation.

President John F. Kennedy announced O’Brien’s appointment as special assistant to the President for congressional relations and personnel on January 2, 1961. O’Brien also was put in charge of scouting for the new administration. During Kennedy’s first year, O'Brien was instrumental in winning votes for the expansion of the House Rules committee in order to ensure a liberal and moderate majority. O’Brien was also responsible for rallying a majority in support of raising the minimum wage. In addition, O’Brien was in charge of handing out patronage; during the 1962 midterm elections, he coordinated President Kennedy’s activities on behalf of the party.

O’Brien remained in the White House following Kennedy's assassination, serving under