Saluri Rajeswara Rao was born in Sivaramapuram near Saluru village of Vijayanagaram District in 1922. His father Sanyasi Raju used to be a mridangam player in the troupe of the legendary violinist Sree Dwaram Venkataswamy Naidu. Rajeswara Rao, a child prodigy, started performing on the stage from the age of four. His father made him train under Sree Dwaram Vekataswamy Naidu for tabla and harmonium. In 1935, Vel Pictures selected him to do the role of Lord Krishna in the film Srikrishna Leelalu. (At that time, most of the films were being shot in Calcutta, and so Rajeswara Rao thus went to Calcutta too for the movie.) Subsequently, he did films like Keechaka Vadha and Uttara Gograhanam. Incidentally, his father played mridangam in all these films. At the same time, Rajeswara Rao was a student of Sree K.L. Saigal for ghazals, of Pankaj Mallik for orchestration, of Faias Khan for Hindustani Classical music, and he eventually returned to Madras and started his own orchestra.

At the age of seventeen, he debuted as music director with the film Jayaprada (1939) but it was the film Illalu (1940) that brought him much name. Gemini Vasan (S.S. Vasan) offered permanent music director position for his films with a salary of Rs. 400/- per month. He did films like Balanagamma, Chandralekha, and others for that banner. Chandralekha which was made in Telugu, Tamil, and Hindi languages got him instant recognition all over the india. The film's drums dances inspried many songs later for so many years. After he came out of the Gemini contract, he did films like Malleeswar, Vipranarayana, and many more memorable films.

Saluri Vasu Rao speaks about his father...
I was very forunate to be his son. He is a very kind and humble person. In all his life, I never saw him getting upset or yelling on anyone that I know. He is a musical genius, I can say. He did a lot of experiments with music even at a tender age! ...He always used to call everyone with one's full name. I never heard him call anyone with a short name, in fact. And, regardless of one's age, he always addressed anyone with the respectful suffix gaaru. For example, I have a friend whom I call Chakri for short, but he used to call Chakri as Chakradhar gaaru, though this guy is my friend and was thus about my age.