[8] On a visit to their sister in Adelaide in 2006, Gadsby entered Raw Comedy in 2006, progressing through the heats to win the national prize.

[14] Gadsby created the stand-up show Nanette, partly as a response to the public debate which took place in Australia before the law was changed to allow same-sex marriage, and also after their diagnosis of autism.

[16] Elahe Izadi of The Washington Post states although Nanette is a comedy, Gadsby insists the audience recognize the dark truth of trauma and assault.

[18][19] In a review for Time Out of their next show Douglas, Ben Neutze wrote, "Yes, it was funny, but Gadsby's main objective was to deliver a fiery and furious takedown of the heterosexual patriarchy.

"[20] According to Mary Luckhurst, writing in Persona Studies, Gadsby's "stand-up has to be set against the epidemic of gender-based violence which continues to infect Australian life and which was declared a 'national crisis' by the Federal Government in 2015.

[27] In Douglas, they discuss their autism diagnosis, aiming to help people understand neurodiversity as part of a normal variation of the human condition.

[30] In July 2021, Gadsby started a solo show, title Body of Work in several venues in Australia, New Zealand, Europe, and the UK.

[32] A review of Body of Work for The Guardian by Brian Logan describes the show as "a winning return for Gadsby, to whose heavy-hitting accomplishments can now be added a flair for comedy with a light heart.

[40][41] Gadsby co-wrote and co-starred in the Australian ABC TV show Adam Hills Tonight through three seasons from February 2011 to July 2013.

They had regular segments called "On This Day" and "Hannah Has A Go" and also featured on the couch, contributing as host Adam Hills interviewed his guests.

[42][43] They co-wrote (with Matthew Bate) and presented a three-part series on ABC, Hannah Gadsby's Oz, which aired in March 2014.

[44] Produced by Closer Productions, this series set out to "debunk the myths of the Australian identity perpetuated by [its] national art".

The exhibition, curated by Gadsby, was meant to explore Picasso's "complicated legacy through a critical, contemporary, and feminist lens, even as it acknowledges his work's transformative power and lasting influence".

[54][55] It was co-curated with Catherine Morris of the Elizabeth A. Sackler Center for Feminist Art and Lisa Small of the Brooklyn Museum.

"[67] Kirkus Reviews described the memoir as a "witty and provocatively written life story" and wrote, "Consistently self-effacing and contemplative, Gadsby acknowledges that [their] unique brand of deadpan observational comedy isn't for everyone, especially since it often skewers 'the two most overly sensitive demographics the world has ever known: straight white cis men and self-righteous comedians.

'"[68] Thomas Floyd wrote in a review for The Washington Post, "For a comic critiqued by some misguided souls as not being funny enough, Gadsby sure understands how to get the last laugh.

"[70] Dana Dunham wrote for the Chicago Review of Books that Gadsby "describes Nanette's inception, its iterations, and its careful layering, representing [their] thinking in actual images of [their] early notes and through artistic metaphor: the shapes of ideas, the palette of thoughts.