The Jeffersons notably addressed LGBTQ+ themes, particularly in later seasons. Episodes like 'And Then There Were None' depicted a gay character with dignity, showing a lead character's journey from prejudice to acceptance. The show used humor to challenge homophobia, contributing to a net positive portrayal for its era.

The Jeffersons featured an episode where George's former business partner, Jimmy, returns as Jenny, a transsexual woman. While George initially reacts with prejudice, the narrative critiques his discomfort and ultimately portrays his reluctant acceptance of Jenny's identity, affirming her dignity and worth.

The show often portrays sincere Christian faith, particularly through Louise and Florence, as a source of compassion and moral guidance. While it satirizes hypocritical adherence (e.g., George's prejudices), the narrative consistently upholds core Christian values and critiques bigotry that goes against them.

The series critiques antisemitic prejudices, often through George's interactions with Jewish characters. The narrative consistently positions the audience to sympathize with Jewish individuals, portraying them with dignity and making George's bigotry appear unfounded and foolish.