Ramakrishnan made the decision to pursue an acting career in her last year at Meadowvale, and got the role in the Netflix teen comedy-drama series Never Have I Ever less than a year after.[4] She deferred her acceptance to the theatre program at York University in Toronto, which she had initially planned to attend the fall after she graduated high school, so she could shoot the series in Los Angeles.[11] In 2021, she deferred her acceptance a second time, while also switching her degree to human rights and equity studies.[12]
Ramakrishnan made her professional acting debut as Devi Vishwakumar, the protagonist, in the Netflix teen comedy-drama series Never Have I Ever.[10][13] In 2019, she was chosen by Mindy Kaling out of 15,000 candidates who had applied for an open casting call for the show.[14] Ramakrishnan created her audition tape at a local library, using her mother's camera, eventually being asked to send four more videos, before having a screen test in Los Angeles and being offered the role.[15] Ramakrishnan was 17 at the time of her casting and had not acted professionally.[15] She revealed in an interview that she grew up watching Indian actor Vijay in the Indian Tamil-language film Pokkiri, which influenced her to consider an acting career.[16] Her casting received significant media attention,[17] especially in Canada,[18] due to the nature of the open casting call and for her Tamil Canadian identity.[19] That year, Today named her one of eighteen "Groundbreakers" on the International Day of The Girl, a list of girls who were breaking down barriers and "changing the world".[20]
In April 2020, Never Have I Ever premiered on Netflix.[21] Ramakrishnan's character, Devi Vishwakumar, an Indian-AmericanTamil high school student, is loosely based on Mindy Kaling.[22] The program ran for four seasons until June 2023.[23] The series and Ramakrishnan's performance received generally positive reviews,[24] with Variety calling it a "breakout performance".[25] She received nominations for an Independent Spirit Award, a Canadian Screen Award, an MTV Movie & TV Award, and two People's Choice Awards.[26] In July 2020, Netflix reported the series had been viewed by 40 million households globally since its release.[27] In May, Ramakrishnan participated in the live-read series Acting for a Cause, appearing as Olivia for a live staged reading of William Shakespeare's play Twelfth Night, to help raise money for a local hospital in Chicago, which was struggling to combat the COVID-19 pandemic.[28] Later that month, she hosted the livestream segment of the Children's and Youth Programming Category for the 8th Canadian Screen Awards.[29] In February 2021, Ramakrishnan was named as Breakout Actor in Time's Time100 Next list of the next hundred influential people.[30]
Ramakrishnan voiced Priya Mangal, an Indian-Canadian mellow, deadpan girl who is one of the protagonist's friends, in the Pixar animated fantasy comedy film Turning Red.[31] The film was released on 11 March 2022 to Disney+ and limited theaters.[32] Ramakrishnan voiced Zipp Storm throughout the content slate for the fifth incarnation of the My Little Pony franchise.[33] The first project, the 2D animated short-form web series, My Little Pony: Tell Your Tale, premiered via YouTube in early April.[34] The series was renewed up to 2026,[35] but prematurely concluded in October 2024, with a two-season run.[36] Ramakrishnan also voiced the character for the animated Netflix series, My Little Pony: Make Your Mark, which premiered in September and was preceded by a special of the same name in May.[37][38] The series ran for six "chapters" until November 2023.[39] Also in April 2022, Ramakrishnan received the honorary Radius Award from the Academy of Canadian Cinema & Television at the 10th Canadian Screen Awards, for her global impact on television.[40][41] In November, she appeared in a Netflix holiday special tied to the Make Your Mark series, titled My Little Pony: Winter Wishday.[42][43] It was followed by the third and fourth specials, My Little Pony: Bridlewoodstock and Secrets of Starlight, in June and November 2023.[44][39] In October 2023, Ramakrishnan had a guest voice role on the adult animated sitcom Big Mouth as Marissa, the new love interest and neighbour of the young fictional version of series co-creator Andrew Goldberg.[45]
Ramakrishnan will star in Freakier Friday (2025); production took place in Los Angeles from June[46] to August 2024.[47] She will be part of a female ensemble—alongside Shirley Chen, Mckenna Grace, Amelie Zilber, Vivian Wu, and Fang Du—in the satirical drama Slanted, from Tideline, a Fox and MarVista Entertainment label.[48] Production began in June 2024 in Atlanta. Ramakrishnan has also committed to co-lead the Netflix romantic comedy film The Netherfield Girls, a contemporary adaptation of Jane Austen's novel Pride and Prejudice.[49]
In October 2020, Ramakrishnan became a global ambassador for humanitarian organization Plan International Canada, to promote girls and women's rights and gender equality.[52][53] She starred in the 2021 campaign for clothing brand Nobis's #NoColdShoulder initiative, which focuses on collecting and donating used jackets every November.[54][55]
In 2022, Ramakrishnan stated that she does not care about labels or the gender of the person that she dates or is in a relationship with, describing herself as "very much so a personality person": "I don't care if you're a boy, girl, or in between".[56]