Defending Jacob features two gay characters, Derek Yoo and Dan Rifkin, both victims of murder. While their sexuality is acknowledged, it is not the central focus or the ultimate cause of their deaths within the narrative's resolution. Their identities are present but incidental to the show's primary themes of crime, justice, and family legacy, resulting in a neutral portrayal.

The character Detective Paul Duffy, who was male in the source novel, is portrayed as Detective Pam Duffy, a female character, in the show adaptation. This constitutes a gender swap for a named, plot-relevant character.

The show adapts the novel 'Defending Jacob,' where characters Lynn Canavan and Sarah Grohl were established as white. In the series, these roles are portrayed by Black and Indian-American actresses, respectively, constituting race swaps.