Godless features a significant lesbian relationship between central character Alice Fletcher and Callie Dunne. Their connection is portrayed with dignity, complexity, and empathy, serving as a genuine aspect of Alice's life and character. The narrative avoids harmful stereotypes, presenting their relationship respectfully within the challenging context of the Old West, contributing positively to the show's character development.

Godless features Martha, a transsexual woman, as a complex and resilient character. The series portrays her with dignity, highlighting her agency in defining her identity despite a traumatic past and societal prejudice. While some characters misgender her, the narrative maintains an empathetic stance, framing her challenges as external forces rather than inherent to her identity.

The series portrays Christianity with nuance, showing both its capacity for solace and community (e.g., the Quaker settlement) and its misuse by hypocritical or violent individuals. The narrative explores themes of redemption and faith without condemning the religion itself, often highlighting virtues like forgiveness and resilience within a Christian framework.