Cissy was born in 1949 as Magdalene Lee. As a teenager, she had an incestuous relationship with her brother Malachi, with the two having sex at a cabin in the middle of the local forest. Their acts were observed by an unidentified woman, known only as the "Appalachian Woman", who was apparently a hermit. Eventually, they accidentally conceived a son together and decided to keep it after panicking about their parents' reaction. When Magdalene finally went into labor at the cabin, Malachi fled in terror and she pursued him into the forest. However, she tripped and wound up being confronted by the Woman, who then assisted her as she gave birth to the baby, on the condition that the Woman got to keep the baby. Although she didn't name it or even kiss it, Magdalene wanted to see it, but upon seeing that it was deformed due to being conceived from incest, she was quick to give it back to the Woman, who called the baby "perfect".
Later becoming very ashamed of everything she had done, Magdalene left the family and briefly went into hiding. When she heard that one of the sons of the Howard family, which had a long-lasting feud with the Lee family, wanted a wife, Magdalene changed her name to Cissy (retaining her birth-name as a middle name) and married the man, hoping to have a fresh new start, apparently later becoming the current matriarch of the Howard family, asserting upon her children (and presumably other relatives) a strict and religious upbringing. She would later use her knowledge of changing one's identity to aid a distant nephew of hers, Caleb Howard, when he tried to leave the Howard family, being ashamed of his heritage.
On March 31, 2014, Clark Howard, Cissy's son from her husband, is murdered after being hanged by barbed wire and having his head twisted completely around. The previous day, Matthias Lee, one of Malachi's sons from his wife (who also butted heads with Clark several times), had also been killed. The day following Clark's death, the BAU bring Cissy in for questioning; she is interrogated by Hotch. During the interrogation, she mockingly congratulates Hotch for his knowledge of the Bible after he describes a biblical character she referenced. She then assertively denies that Clark was responsible for killing Matthias (which was an initial assumption by the BAU), stating that the threatening statements he made against Matthias were merely out of stupidity and that Clark knew he would be punished severely by her if he were to disobey her.
Later, when Maddie Lee, one of Malachi's daughters-in-law, is gruesomely killed in front of her husband, Cissy gives Hotch a list of all the cars owned by members of the Howard family, stating that none of them owned the type of car used to kill Maddie and that no one in the family would dare to kill an innocent woman in the Lee family in spite of the feud. Later, Cissy prays to God in her bedroom, begging him to give her the power she needs to kill whoever is behind the murders. When she hears someone break into the house, she thanks God before taking out a shotgun. Going downstairs, she hears the intruder moving in the kitchen and promptly fires twice from the shotgun, destroying everything in sight, only to find that she has shot at empty air. Cissy is then ambushed from behind, knocked out off-screen, and taken.
She regains consciousness in the shack where she and Malachi made love (although she doesn't recognize it at first), and spots her abductor on the other side of the room. She asks why he took her to the cabin and if he wants money; the man replies that he doesn't want money, but for him to say hello. He then shows her the corpse of a woman, asks her if she recognizes her, and identifies the corpse as his mother. After telling her about how he was raised, the man then tells Cissy he is actually her son conceived with Malachi before declaring that he will decide whether she should live or not, but only after she tells him about what happened. She tries explaining herself, but the man merely retorts that the laws of God or nature can't be changed. Cissy then tells him of the time she went into labor and Malachi subsequently fled, causing her to encounter the Woman, who helped her give birth to the baby.
When the man asks if Cissy named him or kissed him goodbye, she replies no on both questions. When he asks if she ever held him, she answers yes. Then, the man prepares to hang her, despite her protests. However, Cissy tells him that the authorities will find him and that she can give him a way out of it. When he asks why she is helping him, she tells him that she knows she needs to pay for her sins, but she also wants him to live. This causes the man to release her. Off-screen, she provides him with a route of escape, which he successfully uses while she is rescued. By the end of the episode, she encounters Malachi at the elevator of the police station. When he guiltily tells her that he should've been killed, she replies, "It should've been us both." The two then go outside of the police station, where they are confronted by the entire Lee and Howard families, who demand an explanation.