The series was set at an integrated high school in contemporary Los Angeles. While the narrative centered on a dedicated and student-friendly African-American history teacher, Pete Dixon (Lloyd Haynes), it also depended upon an ensemble cast of students and other school employees. The optimistic idealism of Pete, guidance counselor Liz McIntyre (Denise Nicholas), and student-teacher Alice Johnson (Karen Valentine) was balanced by the experienced, somewhat jaded principal, Seymour Kaufman (Michael Constantine). These characters and a handful of other teachers would spend each episode arguing among themselves about the way in which to go about both educating their students and acting as surrogate parents.

A season and a half before Norman Lear made “relevant” programming a dominant genre with the introduction of such programs as All in the Family and Maude, Room 222 was using the form of the half-hour comedy to discuss serious contemporary issues. During its five seasons on the air, the show included episodes that dealt with such topics as racism, sexism, homophobia, dropping out of school, shoplifting, drug use among both teachers and students, illiteracy, cops in school, guns in school, Vietnam War veterans, venereal disease, and teenage pregnancy.

Most importantly, Room 222 served as a prototype of sorts for what would become the formula that MTM Enterprises would employ in a wide variety of comedies and dramas during the 1970s and 1980s. When Grant Tinker set up MTM, he hired Room 222’s executive story editors James L. Brooks and Allan Burns to create and produce the company’s first series, The Mary Tyler Moore Show. This series eschewed issue-oriented comedy, but it picked up on Room 222’s contemporary and realistic style as well as its setting in a “workplace family.” Treva Silverman, a writer for Room 222, also joined her bosses on the new show, and Gene Reynolds, another Room 222 producer, produced The Mary Tyler Moore Show spin-off Lou Grant several years later.

Room 222 was given a number of awards by community and educational groups for its positive portrayal of important social issues seldom discussed on television at the time. It won an Emmy Award for outstanding new series in 1969.