She continued to perform small and extra roles in various other Canadian films, such as Story of Jen (2008),[6] Lick (2010),[7] and A Windigo Tale (2010).

[9][10] Murphy was considering quitting acting as a career path[11] when, in 2013, she auditioned for and got the role of Alexis Rose on the CBC sitcom Schitt's Creek.

[24] In September 2020, she won the Primetime Emmy Award for Outstanding Supporting Actress in a Comedy Series for her performance in the final season of Schitt's Creek.

[27][28] In 2020, Murphy appeared in a holiday advertising campaign for Hudson's Bay department stores opposite her Schitt's Creek co-star Catherine O'Hara.

In 2023, she appeared opposite Salma Hayek in an episode of the Netflix anthology series Black Mirror, titled "Joan Is Awful".

In 2024 and 2025, Murphy starred as the Chief Flavor Officer in an advertising campaign for Talking Rain’s Sparkling Ice, which was developed by marketing company Mod Op.

[33] In January 2021, she donated proceeds from the auction of her first red carpet dress to Encampment Support Network, a not-for-profit that helps Toronto's homeless people.

[1] Murphy has a tattoo of James Stewart's silhouette on her wrist, citing his "heartbreaking, sweet, and funny" performance in Harvey as one of her influences.