Looking out into the audience at her first showcase, Sandra Bernhard recognized a horde of friendly, familiar faces—all smiling as they burst into applause with their impeccably manicured hands.They were Ms. Bernhard’s clients by day—she worked at a nail salon in the heart of Beverly Hills, daydreaming of her big break in show business. She was on the brink, performing stand-up in the 1970s at Ye Little Club, where she met her comedic mentors, Paul Mooney and Lotus Weinstock, during her first performance at age 19.

Dressed in a safari jacket, khaki shorts, a straw hat and a pair of espadrilles, she did a Mary Tyler Moore impression, followed by a bit about being a medium—“This is a small. This is a large. I’m a medium!”

Despite the bad joke, Mr. Mooney and the late Ms. Weinstock took her under their wing. They knew this brassy provocateur was the next big thing.

And, quite frankly, so did she—ever since she was 5 years old.

Born in Flint, Michigan, with an abstract artist for a mother and a proctologist for a father, Ms. Bernhard, who will perform at Guild Hall in East Hampton on Friday, grew up with a relatively balanced view of the world—though that did not dissuade her from her fantasies.

One night, her father’s partner’s wife, while boiling water at the stove, asked her, “What do you want to be when you grow up?”

“I want to be a comedienne,” the little girl answered.

Her declarative aspiration was, rather appropriately, met with a laugh.

“She thought that was so cute,” Ms. Bernhard, now 59, recalled last week during a telephone interview from her home in Manhattan. “I already knew what I wanted to do. I knew I liked entertaining people. I knew I liked making people laugh. People can come into this world knowing what they want.”

Three years later, the young girl found herself at the Fisher Theatre in Detroit watching Carol Channing star in “Hello, Dolly!” as widowed matchmaker Dolly Levi. The 8-year-old was mesmerized and so overwhelmed that she cried the entire way home, because her parents hadn’t arranged a meet-and-greet with the lead actor.

The closest the little girl would get to Ms. Channing’s legacy—until eventually meeting the singer and telling her this series of stories—was just a few months later at her cousin’s bar mitzvah. The band erupted into a rendition of “Hello, Dolly!” and 8-year-old Ms. Bernhard thought they were doing a dreadful job.

So she marched up on stage and grabbed the microphone.

“Let me sing this for you,” she had said.

“Get off the stage,” the band leader ordered, trying to take the microphone back.

And then, from the girl’s flock of dancing family members, her cousin Bernice yelled, “You let her sing this song!”

The band leader immediately backed off. And Ms. Bernhard brought the house down.

“I was a big smash hit,” she laughed, despite herself. “I knew my talent. I had to stake my claim.”

Unsurprisingly for the time—and, to an extent, even today—the comedy world was dominated by men and tough crowds expecting a certain type of entertainment. Ms. Bernhard threw herself into the fire and refused to conform to any standards.

She abides by only one cardinal rule: “Never let them see you crying, Bernhard,” Mr. Mooney had told his young protégé. “That’s what they want.”

Ms. Bernhard never broke in front of an audience. She made her mark on her own terms. And before long, there were enough good nights to make up for the nights “they didn’t really get it,” she said.

“I was telling stories and talking about fashion and beauty,” she said. “And I was not doing self-deprecating material. That was very revolutionary. That’s just who I was. I was part of the post-feminist movement. We all learned to accept ourselves as we were naturally, and not have to get married or depend on men. That world opened up for me, and it became second nature.”

Her act developed into a mix of song, storytelling, cabaret and burlesque—though she will be keeping her clothes on, most likely, during a new version of her show “Sandyland” on Friday night at Guild Hall in East Hampton. In the early 1990s, she caught the attention of the producers behind hit sitcom “Roseanne,” landing the role of Nancy Bartlett in 33 episodes between 1991 and 1997.

The character is one of her best-known, one she has deplored as both a blessing and a curse, because she was among the first actresses to portray an openly lesbian recurring character on American television. Before she knew it, she was a living political statement.

“The whole thing happened very organically, because I was originally married to Tom Arnold’s character,” she said of her co-star. “And he was such a pig, and we thought it would be funny to take the Nancy character and make her gay, in reaction. I don’t think anybody was trying to make some political statement, but it became a big statement because of its naturalistic approach.”

Her “reluctant lesbian icon” reputation drew criticism from the gay community—which Ms. Bernhard shrugged off. Fifteen years ago, she bore a child, Cicely, with her longtime partner, Sara Switzer. They visit the East End at least twice every summer, she said, and their daughter is even showing some interest in comedic writing.

“There’s all sorts of political movements and changes, and because I don’t take a stance in some sort of politically correct way, people are confused or judgmental,” she said. “For me, that just fuels my fire. It makes me even more clear about what I want to say politically. Be how you are, be comfortable in your own skin. If you don’t want to make statements, don’t make statements.”

And to Ms. Bernhard, she said, the way she has lived her life is the biggest statement of all.

Sandra Bernhard and The Flawless Zircons will kick off the inaugural Guild Ha!! Comedy Nights series on Friday, June 20, at 8 p.m. at the John Drew Theater at Guild Hall in East Hampton. Tickets range from $45 to $75. Upcoming performers include Jon Lovitz on Saturday, June 28; John Leguizamo on July 3; and Rob Schneider on August 26. For more information, call (631) 324-0806, or visit guildhall.org.