Reno settled with her family on 20 acres (8 hectares) of wilderness at the edge of the Everglades, outside Miami, Florida, when she was eight years old. There, her parents built the house she would live in for many years to come. Her father, a Danish immigrant, was a police reporter for the Miami Herald and her mother was an investigative reporter for the Miami News. Reno graduated from Coral Gables High School, where she excelled on the debating team, and went on to Cornell University, earning a degree in chemistry in 1960. She then attended Harvard Law School, and, after graduating in 1963, she went to work as a lawyer.

She began her career in politics in 1971 when she was named staff director of the Judiciary Committee of the Florida House of Representatives. In 1973 she was named assistant to the state's attorney general in Miami and became state attorney in 1978. She was reelected to the post five times, even though she was a Democrat in a largely Republican area.

In 1993, after the unsuccessful nominations of two other candidates, President Bill Clinton (Clinton, Bill) nominated Reno for the position of U.S. attorney general, and she was quickly approved by the U.S. Senate. Her early days in office were marked by her efforts to secure greater protection for women seeking abortions, who were often victims of physical harassment from antiabortion activists. Her most controversial early decision, however, was her ordering agents of the Federal Bureau of Investigation (FBI) to conduct the final raid on the compound of the Branch Davidian cult near Waco, Texas. Eighty-six adults and 17 children died as a result of this police action. Reno's acceptance of full responsibility and her candour and obvious regret over the incident helped her earn the respect of many Americans.

Over the next few years, she drafted new legislation broadening the scope of child pornography laws. She clashed with the White House in her efforts to regulate violence on network television, as well as over her refusal to endorse Vice President Al Gore (Gore, Al)'s plan to merge the FBI and the Drug Enforcement Administration. Reno played a leading role in ordering relatives in the United States to return a Cuban child, Elián González, to his father in Cuba after his mother died while attempting to flee to the United States. Reno was among the highest profile cabinet officials, and despite criticism, she appeared on the television show Saturday Night Live, which had a recurring spoof of her while she served in Washington.

In 2002 Reno unsuccessfully sought the Democratic nomination for governor in Florida. Subsequently, she often gave speeches on criminal justice issues in the United States and served on the board of directors of the Innocence Project, which assisted convicted prisoners seek exoneration through DNA testing.