Karthik Raja is the eldest son of musician Mastro Ilaiyaraaja and Jeeva. His brother Yuvan Shankar Raja and sister Bhavatharini, who are also Tamil film music directors and playback singers, have worked with him on notable projects. He did his schooling at St. Bede's School in Chennai and graduated from Loyola College, Chennai. On June 8, 2000, Karthik Raja married Raja Rajeswari at Tirupati, Andhra Pradesh, India.
Born to a family of musicians, he had exposure various kinds of music at a very early age. He had his formal training in Western classical music from the Trinity School of Music, mainly in piano (affiliated with Jacob John). He also had training in Carnatic music from T. V. Gopalakrishnan and Dakshina Murthy Swami. To this day he derives most of his inspiration from classical music (Western and Indian) and jazz..
As a child, he often used to accompany his father to the recording studios. At the age of 13, Karthik Raja played the keyboard for the song Kannukkum from the Tamil movie Ninaikka Therinda Maname (1987). Many such outings followed including playing keyboard for the soundtrack of the movie Nayagan. Karthik also arranged many recordings for his father and composed his first song "Pandianin Rajiyathil" for the movie Pandiyan (1992) and "Ninaikindra" for the movie Athma (1993). Around this time, he also composed some background scores for the TV series Bible.
He debuted as a full fledged composer in 1996 through the Tamil movie Alexander, soon followed by Manikyam. Then came many chart-busters that included Ullaasam, Naam Iruvar Nammaku Iruvar, Kadhala Kadhala and Dumm Dumm Dumm among others. He also debuted in Hindi films with Grahan which won him the R.D. Burman award for the best new talent.