Mama Day centers around the characters George and Cocoa. Cocoa, whose real name is Ophelia, is a young southern woman living in New York who is still deeply connected to her family and ancestry, even though her family's history is fraught with pain and tragedy. George grew up an orphan, overcoming a multitude of challenges in order to finally graduate from Columbia engineering school and co-found his own engineering company.
Cocoa and George meet when Cocoa interviews for job at George's firm. George is unable to hire Cocoa because the job starts immediately and she is obligated to visit Willow Spring Island every August to spend time with Mama Day and her family. Prior to returning to New York from her trip to Willow Springs, Cocoa writes a letter to George saying that she still wants the job. Mama Day intervenes and puts a mysterious substance on the envelope, which causes George to remember Cocoa and soon later recommend her to someone for another job. George and Cocoa begin to date and marry suddenly, but George doesn't visit Willow Springs with Cocoa for four years, during which time Cocoa never shares with him the more unusual and even supernatural aspects of Willow Springs.
After several years they return to Willow Springs together. When George finally does accompany her, being a practical-minded engineer with no family history or special convictions to help him relate to the people of Willow Springs, he has a hard time believing in or understanding some of the events that take place. When he discovers that Cocoa is dying because of a hex put on her by the deeply jealous and hateful Ruby, who is a conjure woman and Mama Day's wicked counterpart, George wants to use practical means to save her life. Just as Cocoa begins to fall ill, a hurricane knocks out the bridge that is connected to the "outside" world, making entering or leaving the island impossible. George and Cocoa are now stuck in Willow Springs, and forced to use the remedies available through Mama Day and the mysticism of the island rather than modern treatment.
The only person that can save Cocoa is George, by following the instructions of Mama Day. However, he is unable to surrender to and believe in the mystical forces that Mama Day has described to him, and when he ultimately tries to take matters into his own hands, it leads to tragic ends.