[4] She has said that her stand-up comedy style has changed drastically since her early days of performing, having initially felt anxious about making jokes about sex and her sexuality due to internalized transphobia stemming from being a trans woman.

"[5] In 2017, Harrison gained wider prominence for her appearance on The Tonight Show Starring Jimmy Fallon, where she made jokes about then-President Donald Trump's ban on transgender people in the military.

Since then, she has appeared in the television shows High Maintenance, I Think You Should Leave with Tim Robinson, Broad City, and Search Party, as well as the film A Simple Favor.

[4] In 2019, she began playing Ruthie in the Hulu comedy series Shrill after the show's co-creator and star Aidy Bryant contacted her through Instagram and encouraged her to audition.

[13] In February 2021, Harrison was banned from Twitter after a stunt in which she impersonated the account of Nilla Wafers in a parody of corporate pinkwashing, and in particular a tweet from the Oreo brand of cookies.

Harrison has said one of her early comedic influences was Mad TV which she enjoyed watching during her childhood and admired the female comedians on the show, especially Mo Collins, Nicole Sullivan, and Debra Wilson.