Eastbound & Down portrays LGBTQ+ characters and themes primarily through the lens of its protagonist Kenny Powers's bigotry. The show frequently uses homophobic slurs, mockery of effeminacy, and prejudiced reactions to gay relationships as sources of humor, often without clear narrative critique, resulting in a net problematic and degrading portrayal.

Eastbound & Down features a trans woman character, Vida, whose identity is primarily used as a source of shock and revulsion for the main character, Kenny Powers. The narrative frames Kenny's transphobic reaction as a comedic element, without offering counterbalance or critique, resulting in a problematic and negative portrayal.

The series satirizes the performative and often hypocritical aspects of Christian culture in the American South, portraying outwardly religious characters as flawed or self-serving. This consistent depiction, without significant counterbalancing nuance, reinforces a negative stereotype of religious hypocrisy.