Nothing is known about Lucille’s life before the apocalypse except that she was married to Negan and was very sick with an unknown illness. Additionally, she was actively being cheated on by Negan. After she died from her illness and reanimated, Negan couldn't bring himself to kill the walker Lucille which he came to see as his one weakness. Negan evidently named his signature weapon, a wooden baseball bat wrapped in barbed wire, after her.
Negan tells Gabriel Stokes about Lucille, calling her his one, true wife that existed before the outbreak. Negan admits his sins in cheating on Lucille and how he couldn't bring himself to kill her after she reanimated. With tears in his eyes, Negan calls his inability to kill the reanimated Lucille his one weakness.
- Illness (Alive)
Lucille was ill for a long time and eventually succumed to her ilness after the apocalypse began due to limited resources. She became a walker and Negan was unable to bring himself to put her down.