He succeeded Harikesanallur Muthiah Bhagavathar as Principal of the Swathi Thirunal College of Music at Thiruvananthapuram, a post he held for 23 years, until the age of 55.

After attending one of his concerts in 1934, Maharani Sethu Parvati Bai of Travancore was so impressed by his talent and scholarship that she invited him to come to Thiruvananthapuram to edit and popularise the compositions of Swati Tirunal. He was instrumental, along with Harikesanallur Muthiah Bhagavathar, for work on the krithis of Maharaja Swathi Thirunal Rama Varma. He was known for producing soulful music, highly creative and yet very orthodox, despite a recalcitrant voice. In 1926, he performed his first music recital at Kumbakonam. At the age of eight he started learning music from his cousin Semmangudi Narayanaswamy Iyer and underwent musical apprenticeship with Maharajapuram Viswanatha Iyer. He lived with his maternal uncle Tirukkodikaval Krishna Iyer, a legendary violin maestro, until the age of four and, after his death, moved to his parents' home in Semmangudi, Thanjavur District. He was born in Thirukkodikaval, Thanjavur District, Tamil Nadu, India, as the third son of Radhakrishna Iyer and Dharmasamvardhini Ammal. He was also considered the 'Pitamaha' or the grand sire of modern Carnatic Music. He was affectionately addressed as 'Semmangudi Maama' (Semmangudi Uncle) by his disciples. He has received many other awards including Padma Bhushan and Padma Vibhushan, from the government of India. He was the youngest recipient of the Sangeetha Kalanidhi, which was awarded to him by the Music Academy in 1947. Semmangudi Srinivasa Iyer (Tamil: ஸெம்மங்குடி ஸ்ரீனிவாச ஐயர்) (JOctober 31, 2003) was considered to be one of the greatest Carnatic vocalists of the twentieth century.

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