Ramans elder brother Chandrasekhara Subrahmanya Ayyar had joined the Indian Finance Service (now Indian Audit and Accounts Service), the most prestigious government service in India. In no condition to study abroad, Raman followed suit and qualified for the Indian Finance Service achieving first position in the entrance examination in February 1907. He was posted in Calcutta (now Kolkata) as Assistant Accountant General in June 1907. It was there that he became highly impressed with the Indian Association for the Cultivation of Science (IACS), the first research institute founded in India in 1876. He immediately befriended Asutosh Dey, who would eventually become his lifelong collaborator, Amrita Lal Sircar, founder and secretary of IACS, and Ashutosh Mukherjee, executive member of the institute and Vice-Chancellor of the University of Calcutta. With their support, he obtained permission to conduct research at IACS in his own time even "at very unusual hours," as Raman later reminisced. Up to that time the institute had not yet recruited regular researchers, or produced any research paper. Ramans article "Newtons rings in polarised light" published in Nature in 1907 became the first from the institute. The work inspired IACS to publish a journal, Bulletin of Indian Association for the Cultivation of Science,' in 1909 in which Raman was the major contributor.
In 1909, Raman was transferred to Rangoon, British Burma (now Myanmar), to take up the position of currency officer. After only a few months, he had to return to Madras as his father died from an illness. The subsequent death of his father and funeral rituals compelled him to remain there for the rest of the year. Soon after he resumed office at Rangoon, he was transferred back to India at Nagpur, Maharashtra, in 1910. Even before he served a year in Nagpur, he was promoted to Accountant General in 1911 and again posted to Calcutta.
From 1915, the University of Calcutta started assigning research scholars under Raman at IACS. Sudhangsu Kumar Banerji (who later become Director General of Observatories of India Meteorological Department), a PhD scholar under Ganesh Prasad, was his first student. From the next year, other universities followed suit including University of Allahabad, Rangoon University, Queens College Indore, Institute of Science, Nagpur, Krisnath College, and University of Madras. By 1919, Raman had guided more than a dozen students. Following Sircars death in 1919, Raman received two honorary positions at IACS, Honorary Professor and Honorary Secretary. He referred to this period as the "golden era" of his life.
Raman was chosen by the University of Calcutta to become the Palit Professor of Physics, a position established after the benefactor Sir Taraknath Palit, in 1913. The university senate made the appointment on 30 January 1914, as recorded in the meeting minutes:Prior to 1914, Ashutosh Mukherjee had invited Jagadish Chandra Bose to take up the position, but Bose declined. As a second choice, Raman became the first Palit Professor of Physics but was delayed for taking up the position as World War I broke out. It was only in 1917 when he joined Rajabazar Science College, a campus created by the University of Calcutta in 1914, that he became a full-fledged professor. He reluctantly resigned as a civil servant after a decade of service, which was described as "supreme sacrifice" since his salary as a professor would be roughly half of his salary at the time. But to his advantage, the terms and conditions as a professor were explicitly indicated in the report of his joining the university, which stated:Ramans appointment as the Palit Professor was strongly objected to by some members of the Senate of the University of Calcutta, especially foreign members, as he had no PhD and had never studied abroad. As a kind of rebuttal, Mukherjee arranged for an honorary DSc which the University of Calcutta conferred Raman in 1921. The same year he visited Oxford to deliver a lecture at the Congress of Universities of the British Empire. He had earned quite a reputation by then, and his hosts were Nobel laureates J. J. Thomson and Lord Rutherford. Upon his election as Fellow of the Royal Society in 1924, Mukherjee asked him of his future plans, which he replied, saying, "The Nobel Prize of course." In 1926, he established the Indian Journal of Physics' and acted as the first editor. The second volume of the journal published his famous article "A new radiation", reporting the discovery of the Raman effect.
Raman was succeeded by Debendra Mohan Bose as the Palit Professor in 1932. Following his appointment as Director of the Indian Institute of Science (IISc) in Bangalore, he left Calcutta in 1933. Maharaja Krishnaraja Wadiyar IV, the King of Mysore, Jamsetji Tata and Nawab Sir Mir Osman Ali Khan, the Nizam of Hyderabad, had contributed the lands and funds for the Indian Institute of Science in Bangalore. The Viceroy of India, Lord Minto approved the establishment in 1909, and the British government appointed its first director, Morris Travers. Raman became the fourth director and the first Indian director. During his tenure at IISc, he recruited G. N. Ramachandran, who later went on to become a distinguished X-ray crystallographer. He founded the Indian Academy of Sciences in 1934 and started publishing the academys journal Proceedings of the Indian Academy of Sciences (later split up into Proceedings - Mathematical Sciences, Journal of Chemical Sciences, and Journal of Earth System Science'). Around that time the Calcutta Physical Society was established, the concept of which he had initiated early in 1917.
With his former student Panchapakesa Krishnamurti, Raman started a company called Travancore Chemical and Manufacturing Co. Ltd. in 1943. The company, renamed as TCM Limited in 1996, was one of the first organic and inorganic chemical manufacturers in India. In 1947, Raman was appointed the first National Professor by the new government of independent India.
Raman retired from IISC in 1948 and established the Raman Research Institute in Bangalore a year later. He served as its director and remained active there until his death in 1970.