Over her four-decade career, Ms. Alley was known for her candidness — whether that involved openly sharing her feelings about weight loss; ardently defending the controversial Church of Scientology, which she belonged to for decades; or giving an off-color speech at the Emmy Awards.

Ted Danson, her co-star on “Cheers,” once called her “a biker chick crossed with an earth mother” and praised her lack of self-consciousness.

“She knows no fear,” Danson told the Los Angeles Times in 1990. “Most of us walk around concerned about how people perceive us, but she is totally unconcerned about that.”

Ms. Alley showed up in Hollywood in 1981 with no training in acting. She became a household name in 1987 after replacing Shelley Long on the sixth season of “Cheers.” Despite limited experience in comedy, she went on to win an Emmy, a Golden Globe and a People’s Choice Award for the part — erasing fears that the departure of the popular Long might tank the show.

In 1994, Ms. Alley earned a second Emmy for her role in the made-for-TV movie “David’s Mother,” in which she played a woman caring for her son with autism.

Soaring ratings coincided with box office victories. “Look Who’s Talking” (1989) earned almost $140 million at the domestic box office, according to the Box Office Mojo tracker. John Travolta, her co-star in that romantic comedy, called their friendship “one of the most special relationships I’ve ever had” in an Instagram post after her death.

Kirstie Louise Alley was born in Wichita on Jan. 12, 1951. She recalled wanting to act since her childhood. “I remember carrying around a picture of Linda Darnell when I was three years old, and I knew that was what I wanted to be,” she told the Saturday Evening Post in 1990, referring to the popular 1940s actress.

Ms. Alley said her name had roots in film. “My mother saw [actress] Loretta Young play a nun, and that’s how I got it,” she told the Tampa Bay Times in an interview published in 1990.

Naturally rebellious, Ms. Alley said she had a rough relationship with her mother while growing up. She attended Kansas State University and the University of Kansas, leaving both before receiving a degree.

Inspired by Doris Day’s character in “Pillow Talk” (1959), she pursued a successful career in interior design and developed an addiction to cocaine. Ms. Alley became sober while participating in Narconon, a drug-treatment program run by the Church of Scientology. She remained a defender of the organization, which has been described as a cult and accused of abuse, throughout her life.

Soon after she moved to Los Angeles, Ms. Alley earned a role in “Star Trek II: The Wrath of Khan” (1982) as Saavik, a Starfleet officer who is mentored by Spock. Her film debut was followed by mostly unremarkable performances before she was tapped for “Cheers” in 1987. While Long’s character, Diane Chambers, was known for her flirty banter, Ms. Alley’s Rebecca Howe was a bold but insecure woman-in-charge and gave a different dynamic to the show.

After “Cheers,” Ms. Alley saw more sitcom success with “Veronica’s Closet” (1997-2000) and later starred in “Fat Actress,” a short-lived 2005 comedy series in which a fictionalized version of Ms. Alley struggles to lose weight.

She was also a spokesperson for Jenny Craig’s weight loss program and in 2011 called out the comedian David Letterman for making jokes about her size when she appeared on “Dancing With the Stars.”

In more recent years, Ms. Alley became known for her comments on Twitter, where she raised questions about the #MeToo movement, downplayed the threat of the coronavirus and touted ivermectin as an unauthorized treatment for the disease. She also publicly supported former president Donald Trump, laying out her political views on “Tucker Carlson Today” in 2021.

Trump wrote Monday on the Truth Social platform that Ms. Alley “was a great person who truly loved the USA” and that she would be missed.

Ms. Alley is survived by her children, True and Lillie Parker. She was married twice and split with her second husband, Parker Stevenson, in 1997.

Ms. Alley’s career and legacy were united by her willingness to be blunt. “I’ve always felt like if someone asks me something, they want the real answer,” she told Good Housekeeping magazine in 2007.

“Usually people think I’m from New York. The only similarity between New Yorkers and Midwesterners is that what you see is what you get.”