Louie Anderson, the genial stand-up comedian, actor and television host who won an Emmy Award for his work on the series “Baskets” and two Daytime Emmys for his animated children’s show, “Life With Louie,” died on Friday in Las Vegas. He was 68.

His death, in a hospital, was confirmed by his longtime publicist, Glenn Schwartz, who said the cause was complications of diffuse large B cell lymphoma, a form of blood cancer.

In an entertainment career that spanned more than four decades, Mr. Anderson had a self-deprecating style that won him legions of fans, among them Henny Youngman and Johnny Carson, whose early support catapulted him to stardom.

In 1981, Mr. Anderson was among the top finishers in a comedy competition hosted by Mr. Youngman, who subsequently hired him as a writer.

Mr. Anderson made his national television debut on “The Tonight Show” with Mr. Carson in 1984, and, as comedians say, he killed. The routine was heavy on jokes about his own weight (which topped 300 pounds at times), and he had the audience roaring from his opening deadpan line: “I can’t stay long. I’m in between meals.”

Afterward, Mr. Carson brought him out for a second bow, a rarity for comics and especially for ones making his debut. As Mr. Anderson told it, Mr. Carson later paid him another high compliment.

“He came by my dressing room on the way to his, stuck his head in and said, ‘Great shot, Louie,’” he told The St. Louis Post-Dispatch in 2002. “Because comics call that a ‘shot’ on ‘The Tonight Show.’ And that was huge for me.”

Mr. Anderson went from earning $500 a week for his stand-up work to making twice that in one night, he said. And film and television work started coming his way, including small roles in “Ferris Bueller’s Day Off” (1986) and “Coming to America” (1988). In 1987, Showtime broadcast a comedy special that captured him in performance at the Guthrie Theater in Minneapolis.

Reviewing the show for The New York Times, John J. O’Connor wrote, “In an age when comedians rely on desperation measures to establish a performing identity — think of Howie Mandel indulging in infantile screaming or Sam Kinison feigning a nervous breakdown — Mr. Anderson has developed a low-keyed act that could fit comfortably into the category of family entertainment.”

He added, “At a time when stand-up comedy is trafficking heavily in insult, hysteria and sexual obsessions, Mr. Anderson seems to have come up with something truly different — old-fashioned, heartwarming humor.”

That would be his bread and butter for his whole career, although he took it in interesting directions. “Life With Louie,” which ran from 1994 to 1998 and won him Daytime Emmys in 1997 and 1998 as outstanding performer in an animated program, was a savvy children’s show that also had an adult following; its title character, a child, dealt with an assortment of problems at home and on the playground.

On “Baskets,” an acclaimed comic drama that ran from 2016 to 2019 and starred Zach Galifianakis, Mr. Anderson, in drag, played the mother of twin brothers played by Mr. Galifianakis. Mr. Anderson was nominated for the supporting actor Emmy for the role three times, winning in 2016.

In a 1996 interview with The Orlando Sentinel, he reflected on his appeal.

“People are comfortable with me onstage,” he said. “There’s nothing hateful about my comedy. I look at it from the humanity standpoint. I’m just kind of like ‘Hey, we’re all in this together,’ and so they feel comfortable inviting me into their living rooms.”

Louis Perry Anderson was born on March 24, 1953, in St. Paul, Minn. His mother, Zella, was a homemaker, and his father, Louis, was a jazz musician.

He graduated from high school in St. Paul and had a job counseling troubled youths when his career path changed as a result of a dare.

“I went out one night with some guys from work and we saw a couple of comedians,” he recounted in a 1987 interview with The Post-Standard of Syracuse, N.Y. “I remarked that neither one of them was very funny, and everybody began telling me to get up there myself if I thought I could do it better.

“The joke kind of escalated over time,” he continued, “and finally one night, I did get up onstage. Once I did, I discovered that I liked it a lot. I have been doing it ever since.”

He began working comedy clubs in Minnesota, then branched out to Chicago and other mid-American cities. At the 1981 Midwest Comedy Competition in St. Louis he did well enough to impress the show’s host, Mr. Youngman, who hired him as a writer and boosted his confidence.

“He helped me learn to write really good material, and he encouraged me to stay in comedy,” Mr. Anderson said of Mr. Youngman. “I was at that point where I wasn’t sure what I wanted to do next.”

The Carson appearance in 1984 helped make him a headliner, and he worked regularly in Las Vegas and other top comedy cities, touring for a time with Roseanne Barr. A 1996 sitcom, “The Louie Show,” on which he played a psychotherapist. lasted only six episodes despite a supporting cast that included Bryan Cranston, but Mr. Anderson frequently played guest roles on other series and was a fixture on late-night talk shows. In the late 1990s and early 2000s, he was host of the game show “Family Feud.”

He was also an author. His stand-up comedy drew heavily on his family in lighthearted ways, but his books had a more serious element. “Dear Dad: Letters From an Adult Child” (1989) was a series of letters addressed to his father that dealt with, among other things, his father’s alcoholism.

“I can remember coming home from school and knowing when I walked in the door whether or not you had been drinking — without even seeing anyone,” he wrote. “That’s how sensitive I think I became.”

As his stand-up career progressed, Mr. Anderson dialed back on the jokes about his weight, and his book “Goodbye Jumbo … Hello Cruel World,” published in 1993, was an honest look at his food addiction. “The F Word: How to Survive Your Family” (2002) and “Hey Mom: Stories for My Mother, but You Can Read Them Too” (2018) also had serious intent.

Mr. Anderson was one of 11 children. His survivors include his sisters Lisa and Shanna Anderson, Mr. Schwartz said.

Mr. Anderson said he based parts of his “Baskets” character on his mother. In “Hey Mom,” he addressed her directly.

“I guess I must believe in the afterlife if I’m writing to you and I talk to you and my face is always turned up to the sky,” he wrote. “If there is an afterlife, I hope there’s a big comfortable chair, because I know you like that, and good creamer for your coffee, and a TV showing old reruns.”

Neil Vigdor contributed reporting.