Rossum grew up in Claremont, California, the oldest child of Ralph and Constance Rossum. Her father was a professor at Claremont McKenna College and her mother worked at Azusa Pacific University. She has two brothers. In 1991, Rossum's father accepted the position of President of Hampden–Sydney College in southside Virginia. The Rossum family moved to Virginia and Kristin enrolled as a a boarding student at the all-girls St. Catherine's School in Richmond, Virginia. While at St. Catherine's, Rossum began using marijuana, drinking beer and smoking. Starting in 1992, Rossum started using methamphetamine.
In 1994, Rossum enrolled part-time at the University of Redlands and moved into a dormitory on campus, but relapsed and left campus, eventually relocating to Chula Vista, a suburb of San Diego. She met Greg deVillers, and, within a year, Rossum appeared to be over her methamphetamine addiction. She enrolled at San Diego State University and graduated with honors in 1998. After graduating, she worked as a toxicologist at the San Diego County medical examiner's office. She and deVillers married in 1999. While married, she had an affair with her boss, Dr. Michael Robertson, beginning in mid 2000.
On November 6, 2000, just after 9:15 p.m., Rossum called 911. Paramedics arrived and found Rossum on the phone in the living room. Her husband, who was unresponsive on the couple's bed that was sprinkled with red rose petals, was pronounced dead on arrival at the hospital. His wife told authorities he committed suicide. The bedroom scene was similar to one in the movie American Beauty.
DeVillers had learned about her affair with Robertson, and discovered she had relapsed into using meth. He had threatened Rossum that he would expose her affair and her drug use to the Medical Examiner's Office if she did not quit her job. Robertson, who also knew Rossum had relapsed, learned of this threat before deVillers was killed. Although it appeared Rossum's suicide ruse had worked well, deVillers' family was suspicious. His brother Jerome was particularly adamant that deVillers was not suicidal. Despite this, San Diego police were reluctant to open an investigation at first. A month after deVillers' death, Rossum and Robertson were both fired – Rossum for hiding her meth habit, and Robertson for hiding his knowledge of Rossum's habit and their affair.
The case took a new turn when the San Diego medical examiner outsourced the autopsy on deVillers to an outside lab in Los Angeles; authorities were concerned about a possible conflict of interest from performing an autopsy on an employee's husband. The tests showed deVillers had seven times the lethal dose of fentanyl in his system. Fentanyl is so rarely prescribed that the Los Angeles lab is one of the few that test for it.
Two weeks after her husband's death, Rossum was interrogated by the police. She told the detectives that her husband had been depressed before he died. Rossum's father stated that he seemed to be deeply distressed and that he drank wine and gin heavily that night. In a television interview months after deVillers' death, Rossum stated, "he was making a big deal of the last rose standing. I think he was just making a statement that he knew our relationship was over." She telephoned his office and told his employers that he would not be coming in to work the day of his murder. While the investigation continued, police learned that Rossum had relapsed and was using meth again.
On June 25, 2001, seven months after deVillers' death, Rossum was arrested and charged with murder. On January 4, 2002, her parents posted her $1.25 million bail.
The prosecution contended that Kristin Rossum killed her husband to keep him from telling her bosses that she was having an affair with the chief toxicologist, Robertson, and that she was using methamphetamine that she stole from the coroner's lab. Defense attorneys argued that Greg deVillers was suicidal and poisoned himself. Kristin Rossum’s brother-in-law, Jerome de Villers, testified that it was difficult to believe his brother had committed suicide because he hated drugs. The emergency 911 tape played in court appeared to indicate Rossum was administering CPR to her husband. According to Rossum's VONS card history, she had purchased a single rose herself.
On November 12, 2002, Rossum was found guilty of first degree murder. On December 12, 2002, Rossum was sentenced to life in prison without the possibility for parole and was taken back to the San Diego jail before being transferred to the Central California Women's Facility in Chowchilla, the largest women's correctional facility in the United States. At her sentencing, the judge ordered Rossum to pay a $10,000 fine.
In 2006, Greg de Villers' family sued Rossum and San Diego County in a wrongful-death suit. On March 25, 2006; a San Diego jury ordered Rossum to pay more than $100 million in punitive damages. San Diego County was ordered to pay $1.5 million. John Gomez, the lawyer for the de Villers family, said that the punitive damages may have been the most ever assessed against an individual defendant in California history. He also acknowledged that the family may never see the money, but wanted to make sure Rossum does not profit from her crime. The family had originally asked for $50 million in punitive damages, but jurors awarded double that amount after estimating Rossum could have made $60 million from selling the rights to her story. A judge later reduced the punitive damages award to $10 million, but allowed the $4.5 million compensatory award to stand.
In September 2010, a three-judge panel of the 9th U.S. Circuit Court of Appeals ruled that Rossum's lawyers should have challenged the prosecution's assertion, by doing its own tests, that Rossum poisoned her husband with fentanyl. The panel ordered a San Diego federal court to hold a hearing into whether the defense's error could have affected the trial's outcome. Rossum had exhausted her state appeals and had turned to federal court.
On September 13, 2011, the U.S. Court of Appeals withdrew its opinion and replaced it with a one-paragraph statement that under a new U.S. Supreme Court precedent Rossum's petition was denied.
Robertson returned to his home in Brisbane, Australia, after being terminated by the medical examiner's office, ostensibly to care for his ailing mother. In September 2013, the San Diego Reader reported that, in 2006, prosecutors secretly filed a criminal complaint charging Robertson with one count of conspiracy to obstruct justice. If he ever returns to the United States for trial, he could face up to three years in prison. He was named as an unindicted co-conspirator in Rossum's 2001 trial. As of 2014, Robertson is running a forensic consulting service in Brisbane.
Rossum was featured in episodes of Oxygen's true crime series Snapped, E!'s Women Who Kill, Investigation Discovery's Deadly Women, Deadly Affairs, and How (Not) To Kill Your Husband.
Her story was also featured on 48 Hours' episode "American Beauty - Was it Murder or Suicide?". In 2004 the case featured on "truTV"s "The Investigators" in an episode titled Pretty Poison.
Caitlin Rother, who was interviewed for each episode, wrote Poisoned Love, a book about the case: ISBN 0-7860-1714-7. Another book about Rossum was Deadly American Beauty by John Glatt: ISBN 0-312-98419-7.