Eastbound & Down includes instances of homophobic slurs used by the protagonist, Kenny Powers, and features a minor character, Catfish, whose implied sexuality is depicted stereotypically and used for crude humor. These elements are presented without significant narrative counterbalance or critique, contributing to a problematic portrayal of LGBTQ+ themes.

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.