She rose to prominence starring in the commercially successful films Toilet: Ek Prem Katha (2017), Shubh Mangal Saavdhan (2017), Bala (2019) and Pati Patni Aur Woh (2019).

For her performances as the septuagenarian sharpshooter Chandro Tomar in Saand Ki Aankh (2019) and a closeted lesbian in Badhaai Do (2022), she twice won the Filmfare Critics Award for Best Actress.

[10][11] Pednekar's acting debut came as the overweight wife of Ayushmann Khurrana's character in the Yash Raj Films-produced and Sharat Katariya-directed romantic comedy Dum Laga Ke Haisha (2015).

[12] Rajeev Masand reviewed, "Pednekar steals the film with an assured turn, effortlessly making you care for Sandhya, without ever reducing her to a slobbering, self-pitying caricature.

[17][18] Two years later, Pednekar was cast in the satire Toilet: Ek Prem Katha (2017) as a young woman in rural India who insists on the eradication of open defecation, opposite Akshay Kumar.

[19] Despite disliking the story, Saibal Chatterjee of NDTV praised her for "flesh[ing] out a refreshingly relatable college topper who becomes the principal catalyst for a mini-revolution".

[21][22] Later that year, her performance opposite Khurrana in Shubh Mangal Saavdhan, a satire on erectile dysfunction, earned Pednekar her first nomination for the Filmfare Award for Best Actress.

[23][24] Reviewing the film for The Indian Express, Shubhra Gupta wrote that Pednekar "once again reminds us just how convincing she can be as a real honest-to-goodness young woman in search of love", but bemoaned that she was being typecast in such roles.

[26] Zoya Akhtar's segment in the Netflix anthology film Lust Stories marked Pednekar's sole screen appearance of 2018; she played a maid who has an affair with her employer.

[31] Udita Jhunjunwala of Mint wrote, "Pannu and Pednekar are wonderful and spunky and embrace their parts even though their body language and posture is variable".

[35][36] Pati Patni Aur Woh, a remake of a 1978 film of the same name and co-starring Kartik Aaryan and Ananya Panday, featured her as a housewife with a philandering husband.

[38] Dolly Kitty Aur Woh Chamakte Sitare, directed by Alankrita Shrivastava and co-starring Konkona Sen Sharma, was screened at the 24th Busan International Film Festival in 2019 and released on Netflix later in 2020.

[48] Rachana Dubey of The Times of India praised the film's handling of LGBT themes and found Pednekar's performance to be "sensitive, nuanced, and on point".

[52] She then appeared in Shashank Khaitan's comic thriller Govinda Naam Mera, co-starring Vicky Kaushal and Kiara Advani, which released on Disney+ Hotstar.

[61] It marked her first project in which she was cast in an urban setting, but she found it challenging to play a character that came close to her own personality, saying that it required "a lot of [my] own demons [...] to be examined".

[62] Comparing her "vibrant comedic performance" to that of stars Carole Lombard and Goldie Hawn, IndieWire's Marya E. Gates found Pednekar's "irrepressible charm" and "overwhelming beauty" to be the highlight in a mediocre film.

[73][74] The journalist Priyanka Roy of The Telegraph wrote in 2019 that Pednekar specialises in playing "women of fortitude with a strong moral fibre, mostly hailing from small towns".