Joyce was disturbed when Angel turned into a stalker after losing his soul and returning to Angelus. She was even more upset when she learned that Buffy had lost her virginity to him. Joyce became increasingly frustrated with the distance between herself and her daughter. When police officers visited the house and informed her that Buffy was a murder suspect, Joyce feared the worst. She met Buffy, who was accompanied by Spike, outside their house. Buffy initially tried to convince her mom that she and Spike were in a band, but when the three were attacked by a vampire, Buffy staked him in front of her mom before leaving to save the world. Joyce reacted badly to this revelation and demanded that Buffy take the time to explain herself, going so far as to warn her not to come back to the house if she left, a statement that she clearly regretted immediately. Taking her at her word, Buffy departed Sunnydale for Los Angeles.While Buffy was gone, Joyce worked with Rupert Giles and the Scooby gang to locate her. She developed a close friendship with Pat, a woman from her book club who was later killed by zombies. Joyce was relieved when Buffy returned and wanted things to go back to normal. She tried to support Buffy's extracurricular activities while also encouraging her to think about her future. After accompanying Buffy on patrol, Joyce fell under a demon's spell, which drove her to lead Sunnydale on a witch hunt. She and others attempted to burn Buffy, Willow, and Amy Madison at the stake and was later horrified at her actions. Spike stopped by the Summers' home when he returned to Sunnydale where Joyce lent a sympathetic ear as he related the details of his recent break-up, which earned his perpetual gratitude.
Joyce's only biological child was Buffy. However, a new daughter, Dawn, mystically appeared in her home. Her existence was interwoven into the everyone's memories. Joyce's health deteriorated and she was diagnosed with a brain tumor (clinically called oligodendroglioma). Pressure from the tumor interfered with her mind and she temporarily lost mental clarity. At that time, Joyce recognized Dawn's anomalous nature and confirmed with Buffy that Dawn was not her daughter by birth. She loved and accepted Dawn as a member of the family and urged Buffy to do everything in her power to protect Dawn.
Joyce's health improved after a successful surgery, although her life was soon in danger again. Glorificus, a hell-god, sought a mystical key that could open inter-dimensional portals. Although Glory did not realize that the key was, in fact, Dawn, she knew that Buffy protected it. She threatened Buffy's family, which forced Joyce and Dawn to temporarily stay with Spike for protection. She continued her friendly relationship with Spike and they watched a soap opera,, together. Soon afterward, Joyce suddenly died from a brain aneurysm which left all of the Scoobies, including Spike, devastated and completely heartbroken.