Despite being offered roles of that of protagonists, Supreeth Reddy has consciously made a choice of playing the role of anti-heroes in movies, which has won him immense praise and recognition. Predominantly seen in Telugu movies, Supreeth made his debut with Teja's 2002 directorial venture Jayam, for which he had missed the auditions but he still managed to find himself in the movie's cast. Following his debut, he was a part of Pawan Kalyan]s directorial debut Johnny in 2003, and was also seen in S. S. Rajamouli's 2004 sports drama Sye.
It was his portrayal of Katraju in Chhatrapati that won him recognition. Although he was seen playing a negative role in the movie, he was initially offered the role of Prabhas' friend. After the success of Chhatrapati, Supreeth received various offers to play the lead role but he declined them all to continue portraying negative roles. In a career spanning close to two decades, Supreeth has successful movies such as Stalin, Neninthe, Ghajini, Billa, Ragada, Dookudu, Rowdy Rathore, 1 - Nenokkadine, and Express Raja to his credit. In 2017, the actor was cast alongside Sachiin Joshi and Esha Gupta in the Tamil-Telugu bilingual murder mystery Veedevadu, which is titled Yaar Ivan in Tamil.