In 1820, while on a charting survey of the eastern Mediterranean, d'Urville helped the French government gain possession of what became one of the best-known Greek sculptures, the Venus de Milo, which had been unearthed on the Aegean island of Mílos in that year. In 1822 he served on a voyage around the world and returned to France in 1825. His next mission took him to the South Pacific, where he searched for traces of explorer Jean-François La Pérouse, lost in that region in 1788. On this voyage he charted parts of New Zealand and visited the Fiji and Loyalty islands, New Caledonia, New Guinea, Amboyna, Van Diemen's Land (now Tasmania), the Caroline Islands, and the Celebes. In February 1828 d'Urville sighted wreckage, believed to be from the frigates of La Pérouse, at Vanikoro in the Santa Cruz Islands. The expedition returned to France on March 25, 1829. The voyage resulted in extensive revision in charts of South Sea waters and redesignation of island groups into Melanesia, Micronesia, Polynesia, and Malaysia. D'Urville also returned with about 1,600 plant specimens, 900 rock samples, and information on the languages of the islands he had visited. Promoted to capitaine de vaisseau (captain) in 1829, he conveyed the exiled king Charles X to England in August 1830.

In September 1837 d'Urville set sail from Toulon on a voyage to Antarctica. He hoped to sail beyond the 74°15′ S reached by James Weddell in 1823. After surveying in the Straits of Magellan, d'Urville's ships reached the pack ice at 63°29′ S, 44°47′ W, but they were ill-equipped for ice navigation. Unable to penetrate the pack, they coasted it for 300 miles to the east. Heading westward, they visited the South Orkneys and the South Shetlands and discovered Joinville Island and Louis Philippe Land before scurvy forced them to stop at Talcahuano, Chile. After proceeding across the Pacific to the Fiji and Pelew (now Palau) islands, New Guinea, and Borneo, they returned to the Antarctic, hoping to discover the magnetic pole in the unexplored sector between 120° and 160° E. In January 1840 they sighted the Adélie coast, south of Australia, and named it for Mme d'Urville. The expedition reached France late in 1841. The following year d'Urville was killed, with his wife and son, in a railway accident.

Dumont d'Urville's chief works include (with others) Voyage de la corvette “l'Astrolabe,” 1826–1829 (1830–34; “Voyage of the Corvette ‘Astrolabe,' 1826–1829”), Voyage au Pole Sud et dans l'Océanie, 1837–1840 (1841–54; “Voyage to the South Pole and in Oceania, 1837–1840”), and An Account in Two Volumes of Two Voyages to the South Seas (1987).