Lori was babysitting with a friend on February 11, 1976 in her hometown of Kettering, Ohio. Her mother dropped off a meal for Lori, her friend and the child they were watching during the evening hours. Lori thanked her and gave no indication anything was amiss at the time. It was the last time Lori's mother saw her daughter. Her mother returned to the residence sometime after midnight and noticed Lori was missing. Lori's friend and the child were asleep; when she awoke, she told Lori's mother that Lori had walked to a convenience store three blocks away to purchase cigarettes. The employee at the business stated that Lori had never arrived at the store that night. She has not been seen again. Her mother searched for in the area with her car, but without success.

One of Lori's friends stated Lori planned to meet a boy that night who said he would take her to California to live with her father. This boy, if he existed, has never been indentified. Lori had a history of running away from home, but before she always phoned her family every time she left to assure them she was fine. She has not contacted anyone since vanishing in 1976. Lori did not take any personal belongings with her and also left her clothing behind at her home. She left a small amount of money untouched in a savings account as well.

Lori's family traveled to California in 1980, four years after she was last seen. They viewed a documentary film regarding the drug angel dust and noticed a girl employed as an extra in the movie who resembled Lori. Her family contacted the filmmakers, Dave Bell Associates, and the producers attempted to identify the young woman. She apparently did not sign a release prior to appearing in the film and has never been identified or located. It is not known if the extra was Lori. Bell's company produced a documentary about Lori's case entitled Whatever Happened To Lori Jean Lloyd?, which was released in the United States in 1981. No solid leads were uncovered after the film aired.

Lori was mistakenly reported to have been found in October 2004. The report turned out to be false and she is still missing. Lori's case remains unsolved.