Midway through her now-legendary stand-up set at Largo in 2012, Tig Notaro stopped to reflect.

“It’s weird because with humor, the equation is tragedy plus time equals comedy. I am just at tragedy right now,” she deadpanned.

Within four months, she had been diagnosed with pneumonia and clostridium difficile, a potentially fatal infection that ate away at her intestines and put her in a hospital for weeks.

She lived to see her 41st birthday—only to endure the death of her mother, who tripped over a lamp, hit her head, and fell into an irreversible coma. Not long after the funeral, Notaro’s girlfriend broke up with her. And then she was diagnosed with breast cancer and underwent a double mastectomy.

It was, to put it lightly, a difficult year.

But on that day at Largo and in the years to come, Notaro found fame in mining humor from grief and the mundane indignities of cancer and death.

She’s been generously open while processing the most hellish year of her life: through fearless stand-up sets showing off her mastectomy scars, a Showtime special, a memoir, and a Netflix documentary, which found the comedian unexpectedly falling in love with, marrying, and trying to conceive—through in vitro fertilization, despite her still-fragile health—with writer and actress Stephanie Allynne.

Happily, the couple is now raising newborn twins. And Notaro is now the subject of her most poignant and profound effort yet: Amazon’s new half-hour comedy One Mississippi.

Prickly, dry, and melancholy-sweet, the six-episode first season loosely re-creates Notaro’s return to her Mississippi hometown after the death of her mother. There we meet her brother Remy (made into a hapless if cuddly symbol of stalled adulthood by Noah Harpster) and her stepfather Bill (John Rothman, who brilliantly turns his terse, emotionally stilted character into a heartbreaking portrait of suppressed grief).

Notaro plays herself, albeit as a radio host ill-equipped for the burden of taking her mother off life support, battling her own sickness, and reckoning with the startling baggage her flawed and free-spirited parent left behind—and the ever-widening gap between who she really was and the beloved images and memories her family clung to for a lifetime.

The result is a sharply written comedy that’s moving, hilarious, compassionate, dark, and, while grounded in reality, prone to surreal flights of dreaminess—a bit like co-executive producer Louis C.K.’s Louie. (In its sometimes-wackiness, it also betrays influence from another executive producer, Diablo Cody, who co-wrote the pilot, then left showrunning duties to Notaro and writer Kate Robin.)

For Notaro, fictionalizing true, traumatic events through a comedic lens is an extension of that “processing” she’s done since 2012. “It sneaks up on me all the time, when and how I process,” she says, sitting across from me in a New York hotel suite, on her first day away from the twins. “Doing this show, I thought because we were fictionalizing so much of it that there wouldn’t be too much. But the woman, Rya [Kihlstedt], who plays my mother is my mother.”

Her eyes go wide and she shakes her head at the memory. “It’s not even, like, somebody doing a great job,” she says. “When she walks on set, I feel like I’m interacting with my mother all over again. Even things that I didn’t live through, that I just went through on set—that’s the part that surprised me. That it would be so emotional when it wasn’t even re-enacting something. It was just a fabricated moment and I felt like I was with my mother. I had a very emotional experience working with her.”

Kihlstedt plays Caroline in dream sequences and flashbacks with a loopy Southern sweetness that fits naturally with what we hear about her: She lived loudly, lovingly, and adventurously, and favored colorful, quasi-psychedelic shirts. All of which makes the sight of her on her deathbed, gasping raggedly for breath hours after doctors turn off the respirator, all the more jarring.

That moment in the pilot perhaps best expresses the show’s canniness at finding humor in the mundanity of grief. Tig sits awkwardly at her mother’s bedside through one false-alarm last breath after another. The sheer unbearableness drives her to hide in the bathroom, where she calls a nurse and complains that her mother can’t breathe (“That’s kind of the point, hun”).

Dazed, she voices what some viewers might already be thinking: She thought people taken off life support “just kind of went to sleep.”

There are flashes of absurd imagery: Tig cheerfully wheeling her dead mother’s body out to the sound of warm cheers from the entire hospital. Tig and the nurse cracking up in raucous laughter after Caroline flatlines and Tig asks, “What now? Do I just leave?”

It’s gruesome and, yes, heartbreaking—but it’s also deeply funny on a basic, relatable level.

“I really don’t know if I would have known how to make a show any other way,” Notaro says. “I like the real and the dramatic element of it. That really speaks to me. But I also love silliness, and I like that there is silliness in the breaks from reality. I can go to both places and I feel like it’s the most real and authentic tone for me.”

“What I love about the show is people can feel like they know my story and they know where it’s gonna go,” she continues. “And that’s been the fun part because it’s not a memoir, it’s not a documentary. Characters are based on people or not based on people. So it’s been nice to present storylines and characters and ideas and then have the writers’ room just run with it.”

Perhaps the season’s most powerful image comes when Tig, whom we’ve watched painstakingly avoid looking down whenever changing out of her clothes, stand in front of a mirror. After a beat of hesitation, she lifts her shirt and stares unflinchingly at the scars on her chest. Notaro has done the same, albeit more triumphantly, in stand-up sets before. But doing it here, she says, was a window to a much more vulnerable time.

“The TV show [moment] is more representative of the real-life moment, because it really took me a long time to look at my body and be OK with myself,” she says. “When I took my shirt off in stand-up, even though that was part of the process and healing, I had way more confidence and security in myself and my body.

“Whereas in the private moment in life, I was still very scared to look at my body. And I think I just wanted to show that, yeah, people see me on TV and in stand-up and interviews, but in the private, quiet moment—there was way more to getting to where I am now.”

One Mississippi coincides with a wave of new shows, including Ava DuVernay’s Queen Sugar and Donald Glover’s Atlanta, that capture the American South with nuance and specificity. For Notaro—who married Allynne in an idyllic hometown ceremony filled with friends, family and neighbors—the show was an opportunity to bring “her” Mississippi, one far removed from regressive bathroom laws and other anti-LGBT discrimination, to television.

“I have so many fond memories of Mississippi and my family and my experiences,” she says. “The openness and love and all that is what I think of when I think of Mississippi, and it’s so beautiful.

“A lot of times people do think it’s just a bunch of barefoot, backwards people,” she continues, “and of course that’s there, but it’s also in upstate New York, it’s everywhere. I wanted to show the world I come from, where my sexuality, my everything is a non-issue. I’m not saying we won’t show other sides, but my Mississippi is not what people have come to know.”

She and Allynne still visit several times a year, she says. Motherhood has kept them busy—and exhausted—but she laughs when I ask how it’s going, her tone a pre-emptive apology for “all the cliché things” she’s about to say.

“It’s all the amazing things. It’s the best time, it’s the best experience, it’s the most important thing,” she says. “It’s exhausting. Last night was the first time I slept through the night in two months. Of course I’m happy to be here doing this, but it was the first time I had to leave them…”

She trails off, heaving a sigh and lifting her hands helplessly. “They’re just these big blobs and it was beyond weird, it was painful to leave. I felt bad leaving Stephanie … But yeah, I went to sleep at 9:30 last night and got up at 8:30.” She grins, guiltily. “It felt good.”

“It’s so weird because every day I wake up and I’m like, I am alive,” she says. “I am healthy, as far as I know, I am happy. I don’t have any want in the world and that wasn’t the case [four years ago]. I thought I was gonna be dead. I had pneumonia, C. diff, and cancer at the same time.

“A friend of mine and I were talking about this recently. If this were 50 years ago, I would have been dead. You can die from all three of those things. It’s definitely weird.”

She stops again to reflect. “I think about it every day.”