Working with President Bill Clinton's administration, Reno directed the world's largest justice and federal law-enforcement office from 1993 to 2001.
At a ceremony to honor Reno in 2009, then-Attorney General Eric Holder praised his predecessor for her tenacity and tireless work ethic during her eight years in the job.
Reno spent her final day at home in Miami before succumbing to complications from Parkinson's disease.
"It's an extraordinary experience, and I hope I do the women of America proud", Reno said after she won confirmation in 1993.
Ms Reno survived the aftermath of the raid to become the longest-serving attorney-general in the 20th Century from 1993-2001 - and one of President Clinton's most trusted cabinet members.
Reno grew up in Miami, where both her parents were journalists, and attended Harvard Law School in the early 1960s.
She was known for deliberating slowly, publicly and in a typically blunt manner.
"I approved the plan and I'm responsible for it", she said at the time.
She always said she made decisions based on evidence and the law. How did Janet Reno die? "All it does is shake and you get used to it shaking after a while", she told a TV interviewer.
Robin Hassler Thompson, a former staff director for the Florida Criminal Justice Committee, explained that she first bumped into Reno in the Florida House; she recalls Reno being a woman that was simply ahead of her time. She was Clinton's third choice, after two other women who were taken out of the running after it was discovered they employed illegal immigrants as nannies.
With negotiations at an impasse, Reno gave the go-ahead for the raid after hearing reports of child abuse in the compound. As a state attorney, she lost a conviction against Miami-Dade County police officers accused of beating a black insurance agent to death; protesters and rioters blamed her for failing to secure the conviction.
Reno's career in the public spotlight came to an end in 2002 after she ran an unsuccessful bid to become the governor of Florida. She also brought a successful anti-trust lawsuit against Microsoft. Obama said that Reno "was tough as nails and never cowered in her fight for what was right".
In 1995 Reno was diagnosed with Parkinson's disease.
Many were outraged by the incident, but Reno was unapologetic.
Reno helped reform the state's juvenile justice system and pursued defaulting fathers for child support payments. But the words she used could have described her entire approach to public life.