[16][17] He appeared in various Hindi films in minor roles, including Bunty Aur Babli (2005), Apaharan (2005), Omkara (2006), Shaurya (2008), Raavan (2010), Aakrosh (2010), Chillar Party (2011), and Agneepath (2012).

Tripathi's first film as a lead actor was the neo-noir thriller Gurgaon (2017), which earned critical acclaim but emerged as a commercial disaster at the Box office.

[20][21] The same year, he also appeared in pivotal roles in several critical and commercially successful films such as the romantic comedy-drama Bareilly Ki Barfi and the comedy Fukrey Returns.

The same year, he starred as Khanna Guruji, a spiritual leader alongside Saif Ali Khan, Nawazuddin Siddiqui, Kalki Koechlin and Ranvir Shorey in the second season of the neo-noir crime thriller Sacred Games (2018–19), which earned him high critical acclaim and a second nomination for the Filmfare OTT Award for Best Supporting Actor in a Drama Series.

He also starred in the Disney+ Hotstar legal drama web series Criminal Justice as a lawyer, and reprised his role in the second (Behind Closed Doors (2020)) and third season (Adhura Sach (2022)).

In 2020, Tripathi starred alongside Chris Hemsworth, Randeep Hooda and David Harbour in his first Hollywood film, the Netflix action thriller Extraction.

The same year, he received dual nominations for the Filmfare Award for Best Supporting Actor for his performances in the biographical drama Gunjan Saxena: The Kargil Girl and the black comedy Ludo.

[29] The same year, he also starred in the ZEE5 biographical comedy Kaagaz (2021), which earned him a nomination for the Filmfare OTT Award for Best Actor in A Web Original Film.

[citation needed] Tripathi met his future wife Mridula during a wedding ceremony in 1993 when they were both in college and then got married on 15 January 2004.

[38] Namrata Joshi of The Wire termed him a "natural actor" and said, "Give Tripathi any role and he will make it his own with his signature style – minimalistic, effortless, unhurried.

"[4] While he had his breakthrough with Gangs of Wasseypur, Tripathi is popular for his portrayal of Kaleen Bhaiya in Mirzapur, which according to The Statesman, has been an inspiration for many aspiring actors.

Raj Nidimoru said, "Given a specific or banal set of instructions, Tripathi would interpret it in a slightly different way and most of the times it would put a smile on your face.

When he finds that perfect note, when he knows he’s got it (and the director knows he’s got it), he holds on to it with such fierce consistency that the slightest shifts only serve to elevate his performance.

[53] The Election Commission of India made Tripathi, the "National Icon" in 2022, to honour his association with ECI in creating awareness among voters.