Marcia Clark was one of the prosecutors in the O.J. Simpson case. On June 12, 1994, O.J. Simpson's ex-wife and the mother of his children Justin and Sydney, Nicole Brown Simpson, and her friend, Ron Goldman, were brutally murdered at Nicole's home while the children slept upstairs. Five days later, O.J. Simpson led police on perhaps the most notorious low-speed chase ever to take place on national television. When the chase ended, police arrested Simpson and charged him with the murders. On July 22, 1994, when arraigned on the charges of murder, Simpson pleaded not guilty. The criminal trial, referred to in the media as the " trial of the century ", began on January 24, 1995, and lasted more than eight months, during which time jurors were sequestered in a nearby hotel to avoid exposure to intense media coverage.

On October 2, 1995, after just four hours of deliberation, the jury, consisting of nine African Americans, two Caucasians, and one Hispanic, reached its verdict. On October 3, 1995, the presiding judge read the verdict, which acquitted Simpson of all criminal charges. Immediately after this unsuccessful prosecution, Clark took a leave of absence. Shortly thereafter, Clark officially resigned from her position as a prosecutor in the Los Angeles County district attorney's office. She was depressed after losing this well-publicized trial, having endured months of criticism during the trial concerning many aspects of her courtroom demeanor. After the Simpson case, Clark had to deal with the fact that, as she puts it, her uninvited celebrity meant that her "old life was gone."

Afterward, Clark coauthored a book on the Simpson trial with writer and Pulitzer Prize winner Teresa Carpenter. Clark is said to have received $4.2 million for the book, Without a Doubt, published by Viking. In addition to writing this book, Clark was chosen to host a television program, LadyLaw, a reality-based examination of the lives of women in law enforcement.