After making his debut in Bala's Pithamagan (2003), Ganja Karuppu experienced success in the late 2000s with his roles in Raam (2005), Sivakasi (2005), Paruthiveeran (2007), Subramaniyapuram (2008) and Naadodigal (2009).

During the period, he was also cast in the second lead role in Chimbudevan's Arai En 305-il Kadavul (2008) alongside Santhanam, produced by S Pictures.

[4][5] In 2012, Karuppu was set to enter Bollywood with a role in the Hindi remake of Samuthirakani's Poraali (2011), but the film eventually did not materialise.

[7][8] Following a period away from notable films, Karuppu made a comeback with significant roles in S. J. Surya's as Isai (2015) and Dharma Durai (2016).

[9] In 2017, he participated in the first season of the Tamil reality television show Bigg Boss hosted by Kamal Haasan.