He graduated with a Bachelor of Science in chemistry from Gurukul Kangri University in Haridwar.[13] Following this, he worked as a chemist in Vadodara for a year, before leaving for Delhi in search of a new job. Once in Delhi, he was instantly drawn to acting after watching a play. In pursuit of securing admission to the National School of Drama (NSD) in New Delhi,[13] he acted in over ten plays with a group of friends, including one in Dehradun,[11] to fulfill one of the criteria for admission.[3]
He made his Bollywood debut in the year 1999 with a small role in the Aamir Khan starrer Sarfarosh.[16] He then appeared in Ram Gopal Varma's 1999 film Shool and the 2000 film Jungle, as well as Rajkumar Hirani's Munnabhai MBBS (2003). After moving to Mumbai, he tried to get work in television serials but did not achieve much success.[17][18] He did a short film, The Bypass, in 2003, where he appeared with Irrfan Khan.[19] Beyond that, between 2002 and 2005, he was largely out of work and lived in a flat that he shared with four other people, surviving by conducting occasional acting workshops.[17] In 2004, which was one of the worst years of his struggle, Siddiqui couldn't pay rent. He asked an NSD senior if he could stay with him. The senior allowed him to share his apartment in Goregaon suburb if he was willing to cook meals for him.[20]
Between 2004 and 2007, Siddiqui had a few minor roles, including in the film Black Friday, which came out in 2007 and was a nominee for the Golden Leopard. In 2009, he appeared in a cameo role in the song "Emotional Atyachar" in the movie Dev D, playing the role of Rangila. He performed a duet with Rasila (known together as Patna ke Presley). In the same year, he appeared in New York. However, it was his role of a journalist in Anusha Rizvi's 2010 film Peepli Live, that first got him wide recognition as an actor.[21] In 2012, he appeared in Prashant Bhargava's Patang: The Kite, which premiered at the Berlin International Film Festival and the Tribeca Film Festival. Siddiqui's performance was praised by film critic Roger Ebert,[22] who stated that the role "transformed his acting style"[23] and he awarded the actor the 'Thumbsup Trophy'. The film was subsequently released in the U.S. and Canada and garnered much attention, with rave reviews from The New York Times.[24]
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[34] and in the Asia Pacific Screen Awards,[35] both in the category of Best Actor. The 2018 film Manto was a groundbreaking performance that won him Best Actor at the 2018 Asia Pacific Screen Awards.[6]
Siddiqui has been married twice. In his youth, he dated a woman named Anjali, who grew up in the same village as he; the couple broke up in 2009.[41] In 2010 or 2011, he married a woman named Sheeba.[41] By 2012, he was dating an American woman named Suzanne.[41] He also had a brief relationship with Niharika Singh, a former Miss India, with whom he co-starred in two films.[41]
Siddiqui eventually reconnected with Anjali, and the couple married and had two children, a daughter and a son. At this point, Anjali took the name Aaliya Siddiqui.[42] In May 2020, Aaliya announced on social media that she was seeking a divorce from Nawazuddin.[43][44]
Siddiqui lives in Mumbai with his younger brother, Shamas Nawab,[45] a film director. When not busy acting, he likes to spend time in his hometown of Budhana, where he owns a farm.[46] In a May 2021 interview, he said that he spends most of his time there.[47]
Siddiqui's first lead role in a feature film was in Prashant Bhargava's Patang, which premiered at the Berlin Film Festival, in which his performance has been praised by film critic Roger Ebert (awarding the film 4/4 stars),[22] who stated that the role "transformed his acting style".[23]