2012–present: Mainstream success
Siddiqui then appeared in the 2012 film Kahaani, in which he played the archetypal short-tempered intelligence officer Khan. Anurag Kashyap's gangster epic Gangs of Wasseypur followed, which furthered the actor's fame. He played his first primary role as Sonu Duggal in Ashim Ahluwalia's Miss Lovely, which premiered at the 2012 Cannes Film Festival, a role Siddiqui describes as his "most real performance so far". Siddiqui then followed this with the sequel to Gangs of Wasseypur. In 2013, he played the lead role in the horror flick Aatma. The Lunchbox premiered as part of the Critics' Week section at the 2013 Cannes Film Festival and won him multiple awards. He appeared in Aamir Khan's 2012 release Talaash. He received the Special Jury Award at the 2012 National Film Awards and the Filmfare Award for Best Supporting Actor in 2013 for The Lunchbox. In 2014, he played the lead antagonist Shiv Gajra in the blockbuster Kick.
In 2015, Siddiqui's films Bajrangi Bhaijaan and Manjhi – The Mountain Man were released, and he was praised for his roles. His work in Raman Raghav 2.0 in 2016 won him the Fancine Malaga Award in Spain and in the Asia Pacific Screen Awards, both in the category of Best Actor. The 2018 film Manto, based on the life of Urdu author Saadat Hasan Manto, won him Best Actor at the 2018 Asia Pacific Screen Awards.
In 2018, Siddiqui starred alongside Saif Ali Khan in Netflix's first original Indian series, Sacred Games, based on Vikram Chandra's novel of the same name.
In 2021, he was seen in the American-Bangladeshi-Indian film No Land's Man.
In 2022, Siddiqui appeared in Heropanti 2.
In 2023, he starred in Afwaah alongside Bhumi Pednekar, in Jogira Sara Ra Ra opposite Neha Sharma, and in Kangana Ranaut's Tiku Weds Sheru, opposite Avneet Kaur.
In 2025, he starred in the Maddock Films production Thamma, alongside Ayushmann Khurrana, Rashmika Mandanna, and Paresh Rawal. He later reprised his role as Inspector Jatil Yadav in the crime thriller Raat Akeli Hai: The Bansal Murders, a sequel to 2020's Raat Akeli Hai. The film, directed by Honey Trehan and written by Smita Singh, premiered at the 56th International Film Festival of India in Goa before its global release by Netflix on 19 December 2025. In 2026, Siddiqui starred in Main Actor Nahin Hoon, directed by Aditya Kripalani.
