[5] In 2012, he directed the action thriller Thuppakki, starring Vijay, which became the second Tamil film to gross ₹100 crore at the domestic box office alone.

[citation needed] His brother, Dileepan made his acting debut with Vathikuchi, which is Murugadoss' production venture.

[citation needed] During his college days, Murugadoss was active in cultural events, particularly in mimicry and drawing.

In 2003, he contemplated making a film titled Varathan with Vikram in the lead role for producer Oscar Ravichandran, but later moved on to other projects.

[10] In 2012, he directed the action thriller Thuppakki, starring Vijay and produced by S. Dhanu released on Diwali 2012 to mostly positive reviews and became the second Tamil film to enter the ₹100 crore club domestically alone[11] after Enthiran.

[12] In 2014, he was the writer and producer for the fantasy film Maan Karate starring Sivakarthikeyan which was directed by his former assistant Thirukumaran.

In 2014, he directed the action drama Kaththi starring Vijay and produced by Lyca Productions released on Diwali 2014 and emerged as one of the top-grossing films in Kollywood for 2014, collecting an estimated ₹131 crores.

[13][14] He joined with Vijay once again for the movie Sarkar which is produced by Sun Pictures Kalanithi Maran which released on 6 November 2018 for the Diwali.