Thenceforward he became a specialist in marine ichthyology, but devoted much time to the investigation, superintendence and exploitation of mines. E. J. Hulbert, a friend of Agassiz's brother-in-law, Quincy Adams Shaw, had discovered a rich copper lode known as the Calumet conglomerate on the Keweenaw Peninsula Lake Superior in Michigan. He persuaded them, along with a group of friends, to purchase a controlling interest in the mines, which later became known as the Calumet and Hecla Mining Company based in Calumet, Michigan. Up until the summer of 1866, Agassiz worked as an assistant in the museum of natural history that his father founded at Harvard. That summer, he took a trip to see the mines for himself and he afterwards became treasurer of the enterprise.
Over the winter of 1866 and early 1867, mining operations began to falter due to the difficulty of extracting copper from the conglomerate. Hulbert had sold his interests in the mines and had moved on to other ventures. But Agassiz refused to give up hope for the mines, and he returned to the mines in March 1867 with his wife and young son. At that time, Calumet was a remote settlement, virtually inaccessible during the winter and very far removed from civilization even during the summer. With insufficient supplies at the mines, Agassiz struggled to maintain order, while back in Boston, Shaw was saddled with debt and the collapse of their interests. Shaw obtained financial assistance from John Simpkins, the selling agent for the enterprise to continue operations.
Agassiz continued to live at Calumet, making gradual progress in stabilising the mining operations, such that he was able to leave the mines under the control of a general manager and return to Boston in 1868 before winter closed navigation.
The mines continued to prosper and in May 1871, several mines were consolidated to form the Calumet and Hecla Mining Company with Shaw as its first president. In August, 1871, Shaw "retired" to the board of directors and Agassiz became president, a position he held until his death.
Agassiz was a major factor in the mine's continued success and visited the mines twice a year. He innovated by installing a giant engine, known as the Superior, which was able to lift 24 tons of rock from a depth of 1,200 metres (4,000 ft). He also built a railroad and dredged a channel to navigable waters. However, after a time the mines did not require his full-time year-round attention and he returned to his interests in natural history at Harvard.
Out of his copper fortune, he gave some US$500,000 to Harvard for the museum of comparative zoology and other purposes.
In 1875 he surveyed Lake Titicaca, Peru, examined the copper mines of Peru and Chile, and made a collection of Peruvian antiquities for the Museum of Comparative Zoology, of which he was curator from 1874 to 1885. He assisted Charles Wyville Thomson in the examination and classification of the collections of the 1872 Challenger Expedition, and wrote the Review of the Echini (2 vols., 1872-1874) in the reports.
Between 1877 and 1880 he took part in the three dredging expeditions of the steamer Blake of the Coast Survey, and presented a full account of them in two volumes (1888).
Of Agassiz's other writings on marine zoology, most are contained in the bulletins and memoirs of the museum of comparative zoology; but he published in 1865, with Elizabeth Cary Agassiz, his stepmother, Seaside Studies in Natural History, a work at once exact and stimulating, and in 1871 Marine Animals of Massachusetts Bay.
Agassiz served as a president of the National Academy of Sciences, which since 1913 has awarded the Alexander Agassiz Medal in his memory. He died in 1910 onboard the SS Adriatic en route to New York from Southampton.