He is best known for his roles as geneticist Mohinder Suresh in the NBC sci-fi drama Heroes (2006–2010), Jai Wilcox in Covert Affairs (2010–2012), Gabriel "Gabe" Lowan in Beauty and the Beast (2013–2014), and Mohan in Never Have I Ever (2020).

In addition, he has appeared on several TV shows, including Ellen, Casualty, Guiding Light, Grey's Anatomy, Ultimate Force, CSI: Miami, Heroes, Covert Affairs and Numb3rs.

Although the character of Mohinder Suresh was originally written for a 55-year-old, his audition tape and screen test were convincing enough for writers to rewrite the part for Ramamurthy.

Ramamurthy guest starred in a season four episode of Psych titled "Bollywood Homicide", directed by his cousin Jay Chandrasekhar.

[9] Ramamurthy joined the cast of the USA Network show Covert Affairs as Jai Wilcox from the second episode onward, replacing character Conrad Sheehan III, played by Eric Lively in the pilot.

[13] On December 19, 2012, it was announced that he would appear in the CW show Beauty & the Beast as Gabriel Lowen, an assistant district attorney.

[15] He reprised his role in the season nine episode "It's My Party and I'll Die If I Want To"[16] As of 2020, he is part of the cast of the Netflix series Never Have I Ever, playing Mohan Vishwakumar, the main character's father.