A long time resident of Greene County, Arkansas, Jimmy Lou Fisher began her political career when she was elected as Treasurer of Greene County in 1970, and went on to serve four two-year terms, until in 1979, when newly elected Governor Bill Clinton appointed her Auditor of State.

Aside from that, she was very active in Democratic politics at the same time. She served as Vice Chairman of the Arkansas Democratic State Committee from 1976 to 1978 and went on to serve as a member of the Democratic National Committee during the same time period, 1976–1978. In 1978, she helped run then Arkansas Attorney General Bill Clinton's ultimately successful run for governor, serving as his 1st Congressional District Coordinator.

Jimmie Lou Fisher served as Auditor of State for one year. In 1980 she ran for state treasurer when Nancy Hall, the first woman ever elected as a statewide constitutional officer in Arkansas, retired after serving 18 years. Fisher easily won the primary due to her powerful connections within the Arkansas Democratic Party. She then went on to win the General Election just as easily, and in doing so, became only the third woman ever to be elected to statewide office in Arkansas (behind Hall and Senator Hattie Caraway). She then went on to win three two-year terms as state treasurer, and four four-year terms, serving a total of 22 years as state treasurer, making her the longest serving state treasurer in the history of Arkansas, and placing her among its longest serving statewide officials.

In 1987 she served as Vice President for the Southern Region of the National Association of State Auditors, Comptrollers and Treasurers. Later, in 1990, she served as President of the National Association of State Treasurers.

Fisher was a very active state treasurer. In 1995 she was a delegate to the White House Conference on Aging, and was later appointed to the Rural Telephone Commission by President Bill Clinton.

While Treasurer, Fisher served as a member of the board of Arkansas Development Finance Authority, the Arkansas Public Employees Retirement System Board, the Arkansas Teacher Retirement System Board, and was a member and Secretary of the Arkansas State Board of Finance.