In 1951, Kennedy joined the Criminal Division of the U.S. Department of Justice. He resigned the following year to run his older brother John F. Kennedy's successful campaign for U.S. senator. In 1953, Robert was appointed one of 15 assistant counsels to the Senate subcommittee on investigations under Senator Joe McCarthy. But later that year, when Democratic members of this subcommittee walked out in protest against McCarthy's harassing methods of investigation, Kennedy resigned.

In 1955, at his own expense, Kennedy joined Supreme Court Justice William O. Douglas on a tour of several Soviet republics. He became chief counsel to the Senate Select Committee on Improper Activities in the Labour or Management Field organized under McClellan in 1957, and he directed a staff of 65.

In 1960, he managed his brother’s successful presidential campaign. When John, as incoming president, appointed Robert as U.S. attorney general, nationwide cries of nepotism arose. Robert's role in his brother's Cabinet was unique. He was virtually the President's other self. Shoulder to shoulder, the brothers stood together—through the Cuban missile crisis, the civil rights cases, and the growing war in Vietnam. Kennedy leaped into the presidential sweepstakes in 1968, abruptly following Eugene McCarthy's solitary effort to dramatize the issue of the war in Vietnam. Kennedy's entrance into the Democratic primaries bitterly divided liberal Democrats. By this time Kennedy, who had come to sympathize with the African-Americans' drive for "black power," was the joy of radical activists. He could reach and unite young people, revolutionaries, alienated African-Americans, and blue-collar Roman Catholics. Meanwhile, the white South hated him; big business distrusted him; and middle-class, reform Democrats were generally suspicious of him.

On the night of June 4, 1968, following a hard-fought, narrow victory in the California primaries, Kennedy was shot by Sirhan Sirhan, a Jordanian immigrant. Kennedy died shortly thereafter in a Los Angeles hospital at the age of 42. Robert Kennedy had been no carbon copy of John. In some ways he was more intense, more committed than John had been, yet he shared his ironic sense of himself and his conviction that one man could make a difference.