Success in Hindi films (2016–2020)
While filming for Running Shaadi, Pannu was approached by Shoojit Sircar for the courtroom drama Pink. She was "curious and excited" about the subject as it had not "been dealt with head-on yet in mainstream cinema". The film, which also starred Amitabh Bachchan, Kirti Kulhari and Andrea Tariang, followed three girls who fight a case against a politician's nephew for molestation. The film and Pannu's performance received positive reviews. Rajeev Masand noted that Pannu, along with other two ladies, "deliver natural performances as strong but emotionally vulnerable women, without a hint of affectation". With worldwide revenue of ₹1.08 billion (US$11 million), Pink emerged as a major commercial success. Pannu later said that the film proved to be a turning point in her career, and earned her the IIFA Woman of the Year award, in addition to her first nomination for the IIFA Award for Best Actress.
Pannu's first release of 2017 was the romantic comedy Running Shaadi opposite Amit Sadh, where she played a Punjabi girl who helps couples in eloping to get married. The film received mixed critical reception but Pannu received unanimous praise for her performance. Following this, she starred in the naval war drama, The Ghazi Attack based on the mysterious sinking of PNS Ghazi during the Indo-Pakistani War of 1971. The film was shot simultaneously in Telugu and Hindi and performed modestly at the box-office. Pannu reprised her role in a spin-off to her film Baby, titled Naam Shabana. Pandey noticed that Pannu's seven-eight minute sequence in the role of special agent Shabana Khan in Baby was well received after which he "decided to give the story an arc". For the role, she trained in different forms of mixed martial arts like Kūdō and Krav Maga. Both the film and Pannu's performance met with mixed response with Sarita A. Tanwar of Daily News and Analysis noting that she is "fantastic in every scene" while Udita Jhunjhunwala of Mint felt that she is "hardly likable" in the film. Pannu's subsequent roles were of a ghost in the Telugu horror comedy film Anando Brahma and the protagonist's girlfriend in the action-comedy Judwaa 2. The latter, which was a reboot of the 1997 namesake film, proved to be commercial success, earning over ₹2 billion (US$21 million). Despite disliking the film, Shubhra Gupta of The Indian Express found Pannu to be the "real surprise" among the ensemble adding that she "makes the most" of an otherwise thinly written part.
Dil Juunglee (2018), co-starring Saqib Saleem, was Pannu's first release of the year. It failed to create an impact among the critics and the audience. Her followup was Shaad Ali's sports drama Soorma which was based on the life of field hockey player Sandeep Singh (played by Diljit Dosanjh). Despite mixed reviews, Soorma became a financial success. Pannu then depicted a lawyer in Anubhav Sinha's legal drama Mulk. Pannu said that the film presents true patriotism and nationalism without taking sides. Pannu's performance was praised with Nandini Ramnath of Scroll.in calling her one of the "strong turns" of the film; the film earned her a first nomination for the Filmfare Award for Best Actress (Critics).
After playing the role of an antagonist in the Telugu action thriller Neevevaro, Pannu played the central role of Rumi Bagga, a free-spirited girl caught in a love triangle, in Anurag Kashyap's romantic drama Manmarziyaan alongside Abhishek Bachchan and Vicky Kaushal. The film premiered at 2018 Toronto International Film Festival to positive critical reviews, with widespread critical acclaim for Pannu's performance. Anupama Chopra called her performance "mercurial, mysterious and maddening": "With her cloud of red hair enveloping her, Rumi seems, continually to be a woman on a warpath". The same year, she also acted in two short films: Baarish aur Chowmein and Nitishastra.
Pannu had a string of releases in 2019, with the first being Sujoy Ghosh's psychological thriller, Badla, an official remake of the 2016 Spanish film The Invisible Guest. It also marked her second collaboration with Amitabh Bachchan. She was initially offered a supporting role and the film had a male lead, however, Pannu convinced the producer to have the lead role played by a female which he agreed to and offered her the role. Badla met with highly positive reviews, as did Pannu's performance as Naina Sethi, a shrewd businesswoman. In her review of the film, film critic Namrata Joshi of The Hindu appreciated Pannu for being "in fine form"; the film met with strong box-office results. Pannu's performance in the film earned the Zee Cine Award for Best Actress (Critics), in addition to her second Best Actress nominations at the annual IIFA and Screen award ceremonies. Pannu then essayed the role of a game designer who uses a wheelchair and battles a home invasion in the psychological thriller Game Over, directed by Ashwin Saravanan. The film was shot simultaneously in Tamil and Telugu language. During the duration of the filming, Pannu had to be in a wheelchair for 12 hours for 25 days. The film and her performance were praised; Saibal Chatterjee said that Pannu "is never less than convincing" and "may be the primary reason why you must go out a watch this film".
She next played an ISRO scientist in the space drama Mission Mangal which was about India's first interplanetary expedition, Mars Orbiter Mission. Pannu accepted a role in the film due to her appreciation of the idea of a space film with, "several leading ladies in it". With a global collection of over ₹2.9 billion (US$30 million), Mission Mangal proved to be one of Pannu's biggest financial successes. Her final film of the year was Tushar Hiranandani's biographical film Saand Ki Aankh, co-starring Bhumi Pednekar. Pannu portrayed the role of Prakashi Tomar, one of the world's oldest sharpshooters for which she underwent three months of training in pistol shooting. Her role was well-received with Anna M. M. Vetticad writing that both Pannu and Pednekar succeed in "delivering equally finely tuned, sensitive performances". Pannu and Pednekar jointly received the Filmfare Award for Best Actress (Critics).
Pannu's sole release of 2020 was Anubhav Sinha's social drama Thappad, where she played the role of Amrita, a home-maker who files for divorce after her husband slaps her. She said that the character's "righteousness, her maturity to handle every situation" made her suffocate. The film and Pannu's performance met with widespread critical acclaim. Shubhra Gupta of The Indian Express noted that she "drives the film" but added that "the effort she puts into her performance shows". Pannu was awarded with the Filmfare Award for Best Actress and received her third nomination for the Filmfare Award for Best Actress (Critics). The film emerged as a moderate commercial success.