One Mississippi is a dark comedy inspired by comedian Tig Notaro's life. Tig returns to her hometown in Mississippi, where she contends with the death of her mother and her own mortality as she embarks on a painful yet hilarious journey that unearths uncomfortable truths about her family and her self.
Hoping to get more intimate with Kate, Tig attends a party at her apartment in New Orleans. Later, Tig and Kate stoke controversy in Bay St Lucille with a discussion on their radio show. Bill is oblivious to the attentions of an admirer, while Remy blows it with a lady friend when a joke leads to a political disagreement.
Tig and Kate deal with negative reactions to their radio show, leading them to a career opportunity. Remy and Bill attend an emotionally charged party at the senior center, while Tig and Kate go fishing and their relationship deepens.
Thwarted in their attempt to deal with their uncomfortable work situation, Tig takes their situation to the airwaves and tells a powerful personal story. Bill attends a wedding with Felicia and makes an impression on her family. Tig supports Bill and Remy, as the men face difficult truths. Tig and Kate go to a new place in their relationship.