The X-Men #1
Professor Charles Xavier runs a school for "gifted" teenagers who are actually mutants — humans born with superhuman abilities due to genetic variation. His first class — Cyclops, Beast, Iceman, Angel, and Marvel Girl — train to be X-Men, a team of heroes who protect a world that fears and hates them. From the first issue, the mutants' persecution is explicit and central to the narrative.
The X-Men created the most enduring civil rights metaphor in popular culture, using the fictional persecution of mutants to explore the dynamics of discrimination based on innate difference. Writers in subsequent decades made the allegory explicit — Chris Claremont in the 1970s-80s developed the anti-mutant movement as a parallel to racism and homophobia in ways that resonated with marginalized readers. The franchise became the most culturally engaged property in superhero comics.
Lee and Kirby created the X-Men in 1963, the same year as the March on Washington, in an America where civil rights were the defining cultural and political issue. The series' premise — hated for an accident of birth they cannot change — was consciously designed as an allegory, though the commercial failure of the original series meant its full social impact was realized only by later writers.
Dr. Fredric Wertham's book "Seduction of the Innocent" triggered a Senate investigation that led to the self-regulatory Comics Code Authority, effectively ending horror, crime, and romance comics and consolidating the market around Code-approved superhero and Western stories. The vacuum left by these dead genres was eventually filled by the underground comix movement of the late 1960s.