Anderson died at a Los Angeles hospital following a "prolonged" illness, her longtime publicist, Cheryl J Kagan said on Sunday.
"We are heartbroken to announce the passing of our dear wife, mother and grandmother," Anderson's family said in a statement.
WKRP in Cincinnati aired from 1978-1982 and was set in a lagging Ohio radio station trying to reinvent itself with rock music.
The cast included Gary Sandy, Tim Reid, Howard Hesseman, Frank Bonner and Jan Smithers, alongside Anderson as the sexy and smart Jennifer Marlowe.
As the station's receptionist, the blonde and high-heeled Jennifer used her sex appeal to deflect unwanted business calls for her boss, Mr Carlson. Her efficiency often kept the station running in the face of others' incompetence.
The role earned her two Emmy Award and three Golden Globe nominations.
Anderson starred on the big screen alongside Burt Reynolds in the 1983 comedy Stroker Ace and the two later married and became tabloid fixtures before divorcing in 1994.
Their son, Quinton Reynolds, was "the best decision that we ever made in our entire relationship", she said during the unveiling of a bronze bust at Reynolds' Hollywood grave site in 2021.
"I think back to the beginning of our relationship, it was so, oh, gosh, tabloidy," Anderson told The Associated Press.
"We were just a spectacle all the time. And it was hard to have a relationship in that atmosphere. And somehow, we did it through many ups and downs."
Anderson detailed their tumultuous marriage in the 1995 autobiography, My Life in High Heels, which she said was about "the growth of a woman, a woman who survives".
"I think if you're going to write about yourself, you have to do it warts and all," Anderson told the AP while promoting the book.
"You may not even tell the nicest things about yourself, because you're telling the truth."
She married four times, most recently to Bob Flick in 2008.
Anderson was born August 5, 1945, in Saint Paul, Minnesota. Her father was an environmental chemist and her mother was a model.
Her first role as an actress was a small part in the 1966 film Nevada Smith, starring Steve McQueen.
Most of her career was spent on the small screen with early guest parts in the 1970s on S.W.A.T. and Police Woman.
After WKRP, Anderson starred in the short-lived comedy series Easy Street and appeared in made-for-TV movies including A Letter to Three Wives and White Hot: The Mysterious Murder of Thelma Todd.
In 2023 she co-starred in Lifetime's Ladies Of The 80s: A Divas Christmas, with Linda Gray, Donna Mills, Morgan Fairchild and Nicollette Sheridan.
"I am heartbroken to hear of the passing of the wonderful Loni Anderson!" Fairchild wrote on X.
"The sweetest, most gracious lady! I'm just devastated to hear this."
Anderson is survived by Flick, her daughter Deidra and son-in law Charlie Hoffman, son Quinton Anderson Reynolds, grandchildren McKenzie and Megan Hoffman, stepson Adam Flick and wife Helene, and step-grandchildren Felix and Maximilian.
A private family service is planned at the Hollywood Forever Cemetery, Kagan said.
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