Godfather of Harlem features a prominent gay character, Teddy Greene, whose identity and relationships are explored with depth and empathy. While depicting the severe prejudice and tragic outcomes faced by LGBTQ+ individuals in the 1960s, the narrative frames these obstacles as external societal forces, affirming the worth of the characters' identities and love.

Godfather of Harlem features Delia, a transgender woman, whose character arc explores a genuine romantic relationship amidst severe societal prejudice and violence in the 1960s. The show portrays her with dignity and agency, framing external bigotry as the source of her struggles. Despite tragic outcomes, the narrative maintains an empathetic stance, affirming the worth of her identity and love.

The show consistently portrays the Black Christian church as a vital community pillar, a source of moral strength, and a foundational base for the civil rights movement. It highlights the faith's role in providing solace, guidance, and a platform for justice in the face of systemic oppression.

Through the prominent depiction of the Nation of Islam and Malcolm X, the series explores the faith's empowering role in fostering Black identity, self-respect, and community activism. While acknowledging internal conflicts and leadership flaws, the narrative largely affirms the positive impact of its teachings on adherents and its significance in the fight against racial injustice.