Having graduated from the prestigious Imperial Alexander Lyceum in 1854, Cassini entered into Government service on 18 December 1854, by joining the Foreign Office in St. Petersburg at age 18.

After 10 years at Dresden, on 17 November 1891, Czar Alexander III appointed him to the key post of envoy extraordinary and minister plenipotentiary to the Chinese Imperial Court at Beijing.

Cassini's time in China was marked by fierce great-power competition as each tried to advance and protect their commercial interests in the Middle Kingdom, and Russia—then constructing the Trans-Siberian Railroad and seeking a warm-water port in the far-East—more so than most.

Then a seasoned diplomat, upon his arrival at Beijing, Cassini took the apparently unprecedented step of refusing to present his credentials to anyone other than the Emperor himself.

Immediately after, and against the efforts of the British Government he was instrumental in arranging for the acquisition for Russia of long term concession of Port Arthur and Talien Bay on the Liaotung peninsula, as well as rights to link these by railroad to Russian lines.

"[6]: 246 Upon the announcement of his dispatch to Washington, the St. Petersburg Novoye Vremya, offered the following appraisal of the Count's tenure in China: Our constant and watchful rival in the far East, England, was at the time still at the very height of her political supremacy in that quarter, and she used her predominance to secure every advantage and create for our Government new difficulties.

At the same time our diplomacy had already outlined those broad historical questions which it was necessary for us to solve in connection with our plans in Asia and the construction of the Siberian line.

Most striking is this state of affairs show in the Anglo Chinese press, which has almost continuously betrayed irritation and intense dislike of Russia's representative at Peking and attributed to him and his Government all sorts of aggressive designs.

[6]: 396  He was seen as being too much of an old school diplomat, and although his adroitness worked well in Beijing, the American Press reported that this was too much the diplomacy of previous generations and as a result, Cassini "as such was unable to secure the confidence of either the people or the government of the United States".

Upon his reaching fifty years of Imperial Service, in 1905, (then aged 68), Cassini received an autographed letter from Nicholas II of Russia and was awarded the Order of Saint Alexander Nevsky.

No known effort was allegedly made on his life, however, it was rumoured that Russian nihilists and pro-Japanese sympathizers were behind the plot and Federal Authorities took it seriously enough for him to be accompanied by armed guards during a trip to the Opera in New York in October 1904.