Alley's children True and Lillie Parker, shared the news in a statement posted to their late mother's Instagram Monday. A representative for Alley confirmed she died of colon cancer to USA TODAY Tuesday.
"We are sad to inform you that our incredible, fierce and loving mother has passed away after a battle with cancer, only recently discovered," read the statement. Alley had not previously disclosed her cancer diagnosis.
"She was surrounded by her closest family and fought with great strength, leaving us with a certainty of her never-ending joy of living and whatever adventures lie ahead," her children said. "As iconic as she was on screen, she was an even more amazing mother and grandmother."
Alley's ex-husband Parker Stevenson wrote on Instagram he was "so grateful for our years together, and for the two incredibly beautiful children and now grandchildren that we have."
Alley's career took off when she starred opposite Ted Danson on "Cheers," the beloved NBC sitcom about a Boston bar, from 1987 to 1993. She joined the show at the height of its popularity, playing Rebecca Howe, the romantic foil to Ted Danson's Sam Malone, after the departure of original star Shelley Long.
Alley's "Cheers" co-star Kelsey Grammer said in a statement to USA TODAY that he "always believed grief for a public figure is a private matter, but I will say I loved her."
In 1991, Alley won an Emmy for best lead actress in a comedy series for the role. She would take a second Emmy for best lead actress in a miniseries or television movie in 1993 for playing the title role in the CBS TV movie “David's Mother."
From 1997 to 2000, she played the title role of a fashion mogul in the NBC comedy "Veronica's Closet," from the creators of "Friends."
She starred alongside John Travolta in 1989's "Look Who's Talking." Travolta paid tribute to Alley on Instagram Monday, calling their relationship "one of the most special" he's "ever had."
"I love you Kirstie," he wrote. "I know we will see each other again."
The 1989 comedy, in which she played the mother of a baby whose inner thoughts were voiced by Bruce Willis, gave her a major career boost. The success of "Look Who's Talking" spawned the 1990 sequel, "Look Who's Talking Too" and the third installment in 1993 "Look Who's Talking Now."
She also played a fictionalized version of herself in the 2005 Showtime series "Fat Actress," a show that drew comedy from her public and media treatment over her weight gain and loss.
She dealt with the same subject matter in the 2010 A&E reality series "Kirstie Alley’s Big Life," which chronicled her attempt to lose weight and launch a weight-loss program while working as a single mother in an unconventional household that included pet lemurs.
Alley said she agreed to do the show, in part, because of the misinformation about her that had become a tabloid staple.
"Anything bad you can say about me, they say," Alley told the Associated Press at the time. "I’ve never collapsed, fainted, passed out. Basically, anything they’ve said, I never. The only true thing is I got fat."
In recent years she appeared on several other reality shows, including a second-place finish on ABC's "Dancing With the Stars" in 2011. She competed on Fox's "The Masked Singer" wearing a baby mammoth costume earlier this year.
She also appeared in Ryan Murphy's black comedy Fox series "Scream Queens" in 2015-16.
One of her co-stars on the show, Jamie Lee Curtis, said on Instagram Monday that Alley was "a great comic foil" on the show and "a beautiful mama bear in her very real life."
In 2020, Alley was criticized for her decision to support then-President Donald Trump for reelection. At the time, she frequently posted on social media about her conservative views and criticized then-Democratic nominee Joe Biden. "He gets things done quickly and he will turn the economy around quickly," Alley tweeted. She was also vocal about CNN's coverage of the COVID-19 pandemic, claiming the cable network was leading viewers to "live in terror."
Alley was also a longtime member of the Church of Scientology.
Alley was born in Wichita, Kansas, to Robert Deal Alley and Lillian Alley. She attended Kansas State University before dropping out and moving to Los Angeles.
Alley was married to her high school sweetheart from 1970 to 1977, and to actor Parker Stevenson from 1983 until 1997.
She told the AP in 2010 if she married again, "I’d leave the guy within 24 hours because I’m sure he’d tell me not to do something."
Alley's children Lillie and William also thanked "the incredible team of doctors and nurses at the Moffitt Cancer Center for their care. Our mother’s zest and passion for life, her children, grandchildren and her many animals, not to mention her eternal joy of creating, were unparalleled and leave us inspired to live life to the fullest just as she did," they added.
"We thank you for your love and prayers and ask that you respect our privacy at this difficult time."
Contributing: Andrew Dalton and Alicia Rancilio, Associated Press
This article originally appeared on USA TODAY: Kirstie Alley, 'Cheers' & 'Look Who's Talking' star, dead from cancer