The series centered on Neil Brock (played by Scott), a New York City social worker who worked for the private agency Community Welfare Service, with his secretary, Jane Foster, played by African-American actress Cicely Tyson. Tyson, notably, wore her hair in cornrows, raising the profile of the hairstyle among African American women. Episodes of East Side/West Side covered topics relevant to the inner city, with many controversial issues explored. A typical example came in the first two episodes, when Brock investigated a prostitute and her child, followed by a story involving statutory rape.
In an effort to open up the number of possible stories, Brock resigned from his job at midseason to work for a New York congressman. The characters played by Elizabeth Wilson and Cicely Tyson soon disappeared and Barbara Feldon was introduced as as Brock's girlfriend. However, despite the high quality of both the writing and acting, the show's penchant for taking on touchy topics forced many potential advertisers to avoid sponsoring the show, while a number of local stations (many in the American South) also chose not to present the program to their viewers.
The show's executive producer, David Susskind, began a letter-writing campaign to government officials, newspaper editors and other prominent individuals. Susskind's request was an attempt to elicit positive feedback to encourage renewal of the series. However, the effort failed when the show was cancelled on January 28. In 1964, the series received eight Emmy Award nominations, including one win for Outstanding Directorial Achievement for the controversial November 4, 1963 episode entitled, "Who Do You Kill?" The episode, which also garnered a writing nomination, as well as acting nominations for supporting actors James Earl Jones and Diana Sands, explored the aftermath of an African-American child's death from a rat bite in a Harlem slum.