After a series of box-office failures, he achieved success with the romance films Ishq (2012) and Gunde Jaari Gallanthayyinde (2013), receiving Filmfare Award for Best Actor – Telugu nominations for both these performances.

Nithiin went onto further establish himself with notable films such as Heart Attack (2014), Chinnadana Nee Kosam (2014), A Aa (2016), Bheeshma (2020), and Maestro (2021).

He then enquired him about his acting interest and did a screen test and photo session, after which, he selected him as the lead for Jayam,[7] which also starred Sadha and Gopichand.

Like Jayam, it went to become a big blockbuster, becoming the third-highest grossing Telugu film of the year, after Simhadri and Okkadu.

In 2004, Nithiin starred in Sri Anjaneyam, directed by Krishna Vamsi, where he played the role as a devotee of Lord Hanuman.

[14] In Ishq, Nithiin paired opposite Nithya Menen, which was also co-produced by his father Sudhakar Reddy.

[20][better source needed] Nithiin acted in the film A Aa (2016), written and directed by Trivikram Srinivas, opposite Samantha Ruth Prabhu and Anupama Parameswaran.

[23] In 2018, Nithiin's Chal Mohan Ranga directed by Krishna Chaitanya with co-star Megha Akash.

His 2020 film Bheeshma, directed by Venky Kudumula and starring alongside Rashmika Mandanna was a commercial success.

[25] Nithiin collaborated with director Chandra Sekhar Yeleti for Check (2021), co-starring Rakul Preet Singh and Priya Prakash Varrier.

His second release of the year was Rang De, directed by Venky Atluri and starred alongside Keerthy Suresh.