Smith played an active role in JFK's 1960 presidential campaign, and was working as Kennedy's campaign manager for re-election in 1964 at the time when President Kennedy was assassinated in Dallas, Texas on November 22, 1963. Smith served as United States Senator Robert F. Kennedy's campaign manager during his 1968 presidential run at the time when the Senator was assassinated at the Ambassador Hotel in Los Angeles, California on June 5, 1968. In the fall of 1979, as polls showed that Senator Ted Kennedy could easily defeat President Jimmy Carter in the Democratic primaries, Kennedy announced his candidacy and made Smith his campaign manager. Kennedy lost to Carter and chose to not run again.