Pothineni first appeared in Tamil language short film Adayaalam (2002) where he played an 18-year old drug addict. He then made his theatrical debut in 2006 with Devadasu. His second film, Jagadam opposite Monalisa was directed by Sukumar. He then appeared in Ready alongside Genelia D’Souza directed by Srinu Vaitla which was a commercial success. In 2009, he had two releases, Maska and Ganesh: Just Ganesh. In 2010, Pothineni had only one release, Rama Rama Krishna Krishna, produced by Dil Raju and directed by Srivaas.

Pothineni’s next film was Kandireega (2011). Later he starred in Endukante… Premanta! (2012) alongside Tamannaah, directed by Karunakaran and produced by Sravanthi Ravi Kishore. In 2013, Pothineni appeared in Ongole Githa with Kriti Kharbanda directed by Bhaskar and produced by B.V.S.N. Prasad. In the same year, he co-starred alongside Venkatesh in the action comedy Masala, the remake of the Hindi film Bol Bachchan, directed by K. Vijaya Bhaskar and jointly produced by Sravanthi Ravi Kishore and D. Suresh Babu.

In 2015, Pothineni starred in two films, Pandaga Chesko and Shivam . While Pandaga Chesko directed by Gopichand Malineni, was a commercial success, while Shivam ended up as one of the biggest failures of his career. In 2016, He had two releases, both produced by his own production house Sri Sravanthi Movies, Nenu Sailaja which was a commercial success and Santosh Srinivas-directed Hyper which failed at the box office.

His 2017 coming-of-age film Vunnadhi Okate Zindagi received mixed reviews. In 2018, he starred in the romantic comedy Hello Guru Prema Kosame directed by Trinadha Rao Nakkina. In 2019, he collaborated with director Puri Jagannadh for the action thriller iSmart Shankar. Pothineni tasted success with the film after a series of flops. It grossed over ₹75 crore, his career’s highest grosser.