Friend and manager Lupe De Leon said the R&B legend died early Friday at Riverside Community Hospital with her husband and two sons by her side.
Born Jamesette Hawkins in Los Angeles, the powerhouse singer had a career that spanned more than 50 years. As a child, she began singing in church in South Los Angeles and signed her first record deal as a teenager.
But it's for her tender ballad "At Last" that she will best be remembered. The song defined her career.
Over the years, brides used it as their song down the aisle and car companies to hawk their wares. Perhaps most famously, President Barack Obama and the first lady danced to a version at his inauguration ball.
James won four Grammy Awards during her long-running career, and she is also a member of the Rock and Roll Hall of Fame. In 2003, she received her own star on the Hollywood Walk of Fame. Friday, flowers and mementos from fans graced that star.
While she achieved great fame, there was also great heartache. The music pioneer spent years battling an addiction to drugs, including heroin, that she admitted took away some of her talent.
She overcame her addictions and resurrected her career with a series of successful jazz recordings.
In her last television appearance, James reprised her signature song in a live performance on "Dancing With The Stars."
In her autobiography, James wrote, 'I wanted to be rare, I wanted to be noticed, I wanted to be exotic as a Cotton Club chorus girl, and I wanted to be obvious as the most flamboyant hooker on the street. I just wanted to be."
Terry Stewart, the president of the Rock and Roll Hall of Fame, said her ever-changing sound has influenced rock and roll, rhythm and blues, pop, soul and jazz artists, marking her place as one of the most important female artists of our time.
Beyonce, who played James in the 2008 movie, "Cadillac Records," paid tribute to James with a post on her website:
"This is a huge loss. Etta James was one of the greatest vocalists of our time. I am so fortunate to have met such a queen. Her musical contributions will last a lifetime. Playing Etta James taught me so much about myself, and singing her music inspired me to be a stronger artist. When she effortlessly opened her mouth, you could hear her pain and triumph. Her deeply emotional way of delivering a song told her story with no filter. She was fearless, and had guts. She will be missed."
Before she died, James suffered from dementia, kidney problems and the leukemia that would claim her life.
The Associated Press contributed to this report.