Naidu's first professional acting job, which he won from an open call, was a leading role opposite Michael Keaton in the 1986 filmTouch and Go (1986). This was followed by anABC Afterschool Specials (1972) episode,No Greater Gift (1985), where he played Nick Santana, a 12-year-old boy with a terminal illness. Naidu then appeared in theMacGyver (1985) TV series' first-season episode,To Be a Man (1986) in 1986.

Other early film credits includeWhere the River Runs Black (1986) opposite Charles Durning andVice Versa (1988). Between 1988 and 1995 he worked extensively in classical theatre.

Naidu returned to film acting in 1996 with Richard Linklater'sSubUrbia (1996), for which he was nominated for the Independent Spirit Award for Best Supporting Male and competed against the likes of Samuel L. Jackson, Roy Scheider and Jason Lee.

On screen, Naidu starred in the cult filmRisutora man (1999), as well as appearing in such films asK-PAX (2001),SUBWAYStories: Tales from the Underground (1997),Requiem for a Dream (2000),Bad Santa (2003),The War Within (2005),The Guru (2002),Waterborne (2005), andLoins of Punjab Presents (2007). He co-starred as a series regular in the sitcomLateLine (1998) and had guest starring roles on the television dramasThe Sopranos (1999),The White House (1999), andBored to Death (2009).

Naidu has been working extensively with musicians from the Asian underground music movement for many years as a breakdancer and an M.C. His vocals have appeared on many records, most notablyTalvin Singh's mercury award winner "OK".

In 2006, Naidu directed his first feature filmAshes (2010) which had its release in 2010 and for which he won Best Actor accolades from the MIACC Film Festival in New York and the London Asian Film Festival.

Naidu's most recent theatre credits include The Kid Stays in the Picture at the Royal Court Theatre, The Master and Margarita with Complicite, a world tour of Shakespeare's Measure for Measure with Complicite, The Resistible Rise of Arturo Ui alongsideAl Pacino, directed bySimon McBurney and The Little Flower of East Orange alongsideEllen Burstyn at New York's Public Theater directed byPhilip Seymour Hoffman. In 2001 Naidu's solo theatre piece Darwaza was a sold-out hit at New York's Labyrinth Theatre.