Drunk History frequently features LGBTQ+ historical figures, integrating their stories respectfully into broader narratives. While the show's comedic tone comes from the drunken narration, the reenactments consistently portray these characters with dignity, highlighting their achievements and the external societal challenges they faced. The overall portrayal is affirming, bringing diverse queer histories to a wide audience.

Drunk History features a segment on Christine Jorgensen, a pivotal trans woman. While presented with the show's characteristic comedic narration and re-enactment, the segment highlights her pioneering spirit, agency, and historical impact. The portrayal, despite its humor, ultimately affirms the worth of her life and contributions.

Drunk History frequently features actors portraying real historical figures of the opposite gender for comedic re-enactment, which aligns with the definition of a gender swap.

Drunk History re-enacts historical events using actors to portray real historical figures. The show frequently casts actors of a different race than the documented historical figure, which constitutes a race swap.

The show frequently lampoons historical figures and institutions associated with Christianity, portraying them through the lens of unreliable, drunk narrators who highlight their perceived foolishness, hypocrisy, or cruelty for comedic effect. The narrative offers no significant counterbalancing positive portrayal or nuance.