She died Thursday morning of pancreatic cancer of the neuroendocrine type, according to a statement from her publicist, Gwendolyn Quinn.
Her family released the following statement:
"In one of the darkest moments of our lives, we are not able to find the appropriate words to express the pain in our heart. We have lost the matriarch and rock of our family. The love she had for her children, grandchildren, nieces, nephews, and cousins knew no bounds."
"We have been deeply touched by the incredible outpouring of love and support we have received from close friends, supporters and fans all around the world. Thank you for your compassion and prayers. We have felt your love for Aretha and it brings us comfort to know that her legacy will live on. As we grieve, we ask that you respect our privacy during this difficult time."
Franklin had been struggling with health problems in recent years. Earlier in the week it was confirmed that she was seriously ill and was surrounded by friends and family in her Detroit home.
The legendary vocalist was perhaps best known for "Respect" - the Otis Redding cover that her powerful voice transformed into a bold anthem and demand for dignity adopted by the feminist movement in the 1970s.
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She also had a string of 20 No. 1 R&B singles, stretching from 1967 to 1985. Those iconic tunes helped earn her 18 Grammy Awards and consistently placed her on most critics' lists of the greatest singers of all time.
In 1987, Franklin became the first woman inducted into the Rock & Roll Hall of Fame.
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She performed at the inaugurations of three presidents - Jimmy Carter, Bill Clinton and Barack Obama.
President George W. Bush presented Franklin with the Presidential Medal of Freedom in 2005.
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Last year, the icon announced her plans to retire, saying she would perform at "some select things."
One of those select events was a gala for Elton John's 25th anniversary of his AIDS foundation in November in New York City, where Franklin closed the event with a collection of songs including "I Say a Little Prayer" and "Freeway."
Franklin canceled planned concerts earlier this year after she was ordered by her doctor to stay off the road and rest up. She was originally scheduled to perform on her 76th birthday in March in Newark, New Jersey, and at the New Orleans Jazz and Heritage Festival in April.
As news of her death was learned, everyone from world leaders to Hollywood icons to fellow music industry legends reflected on her life and legacy.
Aretha helped define the American experience. In her voice, we could feel our history, all of it and in every shade—our power and our pain, our darkness and our light, our quest for redemption and our hard-won respect. May the Queen of Soul rest in eternal peace. pic.twitter.com/bfASqKlLc5— Barack Obama (@BarackObama) August 16, 2018
Let’s all take a moment to give thanks for the beautiful life of Aretha Franklin, the Queen of our souls, who inspired us all for many many years. She will be missed but the memory of her greatness as a musician and a fine human being will live with us forever. Love Paul pic.twitter.com/jW4Gpwfdts— Paul McCartney (@PaulMcCartney) August 16, 2018
The Associated Press contributed to this report.