One of the last students of G.D. Cassini (Cassini I, 1625-1712), Delisle graduated and later taught mathematics and astronomy at the College de France. From 1710 to 1715, he set up an observatory on the Palais de Luxembourg, but later had to move his equipment to Hotel Taranne.
In 1724 he travelled to England and was received into the Royal Society, and among others met famous Isaac Newton. Following an invitation of Tzar Peter I of 1721, after some hesitation, he finally went to St. Petersburg in 1725, together with his younger brother Louis and an instrument maker named Vignon. He stayed in Russia for 21 years, and was a member of the Emperial Academy of Sciences as well as director of the St. Petersburg Observatory. For some time, he undertook wide travels throughout Russia and Sibiria to do survey work. Louis de la Croyere Delisle travelled even further to Eastern Sibiria, where he eventually died on sea off the coast of the Kamtchatka peninsula in 1741, and was buried near Avacha, next to Lt. Charles Clerke, on the Kamchatka peninsula.
Joseph Nicolas Delisle returned to Paris in September 1747, where he resumed his chair of astronomy in the College de France. Among his students was Jerôme de Lalande.
In Paris, Delisle took residence in Hôtel de Cluny (or Clugny, as it was spelled at that time). He set up a small observatory on the tower of this building, had a secretary named Libour, and engaged the young Charles Messier in late 1751 as a copist, then as a depot clerk and observing assistant. Under his directions, Messier longly looked for the expected Comet Halley without success, because of erroneous and mismanaged directions by the then over 70-year-old Delisle. Later he seems to have changed his attitude on Messier, and eventually retired in 1765.
Joseph Nicolas Delisle died of apoplexy in Paris on September 12, 1768 at age 80.
He was honored by naming a Moon Crater after him (29.9 N, 34.6W, 25.0 km diameter, in 1935).