Other characters featured in the show include the school's compassionate guidance counselor, Liz McIntyre (Denise Nicholas), who is also Pete's girlfriend; the dryly humorous school principal, Seymour Kaufman (Michael Constantine); the petite and enthusiastic Alice Johnson (Karen Valentine), who is initially a student teacher, later full-time teacher whom Pete mentors; and Principal Kaufman's secretary, Miss Hogarth, played by Patsy Garrett.

The themes of the episodes are sometimes topical, reflecting the contemporary political climate of the late 1960s and early-to-mid 1970s, such as the Vietnam War, women's rights, race relations, and Watergate.

", a student is a mistaken victim of anti-gay harassment, while the 1974 episode "I Didn't Raise My Girl to Be a Soldier" delves into parent–teenage child issues.

[2] Notable guest stars during the series five-season run include Larry Linville, Cindy Williams, Chuck Norris, Nancy Wilson, DeForest Kelley, Rob Reiner, Richard Dreyfuss, Burgess Meredith, Kurt Russell, Aretha Franklin, Bernie Kopell, Mako, Angela Cartwright, Ed Begley Jr., Dabney Coleman and Mark Hamill.

Exterior shots of Los Angeles High School, pre-1971 earthquake, were shown in the opening credits, and some outdoor scenes in the early seasons.

However, while Room 222 is a comedy drama, milder in tone, Halls of Anger is purposefully aggressive, using deliberately controversial language and some forceful violence to highlight the real and dangerous potential of unresolved racial conflict.

The Television Academy Foundation has credited Room 222 for not only in the way it portrayed a racially integrated classroom and revolved around "a dedicated and student-friendly African-American history teacher," but also for predating Norman Lear's 1970s sitcoms when it came to invoking serious social issues, stating that "A season and a half before Norman Lear made "relevant" programming a dominant genre with the introduction of programs like All in the Family and Maude, Room 222 was using the form of the half-hour comedy to discuss serious contemporary issues.

[7] According to the Television Academy Foundation, "the show broke new narrative ground that would later be developed by the major sitcom factories of the 1970s, Grant Tinker's MTM Enterprises and Norman Lear's Tandem Productions.