Leonhart was appointed as a DEA Special Agent in late 1980, and was first assigned to Minneapolis, Minnesota, where she worked for five years. In 1986, Leonhart transferred to the St. Louis Field Division where she became the Special Agent recruiter for the division. She was promoted to a GS-14 Group Supervisor position in the San Diego Field Division in early 1988. After a short assignment as the supervisor of an intelligence group, she supervised an enforcement group for five years.
Leonhart was featured in a documentary filmed by the BBC in 1991. Her enforcement group conducted numerous investigations to include international smuggling cases. The most notorious of her group's investigations was the investigation of a major Bolivia-based cocaine cartel that resulted in the arrest and conviction of cartel leader Jorge Roca-Suarez, co-defendants, and the seizure of over $14 million in assets. Leonhart was awarded the DEA Administrator's Award in 1993 for her distinguished service as a group supervisor.
In 1993, Leonhart transferred to DEA Headquarters in Arlington, Virginia, where she served as an (internal affairs) inspector with the DEA Office of Professional Responsibility (OPR). In 1994, Leonhart was promoted to GS-15 and served on DEA's Career Board until her assignment as Assistant Special Agent in Charge of the Los Angeles Field Division in 1995. In 1996, she was promoted to the ranks of the Senior Executive Service (SES) and was assigned oversight of the Special Agent Recruitment Program at DEA Headquarters. Leonhart was appointed in 1997 as the Special Agent in Charge (SAC) of the San Francisco Field Division, where she served until her appointment in September 1998 as the SAC of the Los Angeles Field Division. In that capacity, she commanded DEA offices and enforcement operations in the Los Angeles area, as well as Nevada, Hawaii, Guam, and Saipan. She remained in this position until 3 September 2003, when President Bush announced his intention to designate Leonhart as Acting Deputy Administrator.