Kalinnikov was born into a family of officials and received his education at the Oryol Spiritual Seminary, where he began studying music and led a choir for some time. His younger brother, Viktor Sergeyevich, also became a composer.

In 1884, he enrolled in the preparatory classes at the Conservatory, but due to a lack of funds for tuition, he was soon expelled. However, he managed to enter the Musical and Dramatic School of the Moscow Philharmonic Society, where he studied bassoon and composition until 1891. Among his teachers were S. N. Kruglikov, A. A. Ilyinsky, and P. I. Blahamberg. Kalinnikov also attended lectures by V. O. Klyuchevsky at Moscow University.

Due to a lack of stable income, Kalinnikov had to play in theater orchestras on violin, bassoon, or timpani and copy sheet music. He was supported by music critic Semyon Kruglikov, and Pyotr Tchaikovsky, highly appreciating his talent, recommended him for the position of conductor at the Maly Theater in 1892. At that time, Kalinnikov also gave private lessons in music theory and singing.

In the fall of 1893, he began to show symptoms of tuberculosis and moved to Crimea, where he spent the remaining years of his life, continuing to compose music. He passed away on December 29, 1900 (January 11, 1901) and was buried at the Polikurovsky Cemetery in Yalta. His gravestone is engraved with the notes of the main theme of his First Symphony in g minor.

Kalinnikov's style continues the traditions of Russian musical classics, including the composers of the 'Mighty Handful' and P. I. Tchaikovsky. His most famous work, the First Symphony in g minor, written in 1895 and dedicated to Kruglikov, premiered at a concert of the Russian Musical Society in Kyiv and quickly became popular both in Russia and abroad.

In Kalinnikov's overture 'Bylina,' there is a theme whose initial measures coincide with the melody of the USSR anthem, which has led to speculation that Alexandrov is not the true author of the modern anthem of Russia. The exact time of the overture's creation, usually attributed to 1893, is unknown: it was not performed during the composer's lifetime and was reconstructed from orchestral parts preserved in the State Central Museum of Musical Culture. It was first broadcast on the radio on July 26, 1950, by an orchestra conducted by S. Gorchakov, and the score was published in 1951. There is no information that the author of the Soviet anthem could have accessed 'Bylina' in the archive.