[4] While working at the observatory, Nicollet discovered a comet and built a reputation as an expert in astronomy and physical geography.

Nicollet encountered financial and professional difficulties resulting from political turbulence in France following the July Revolution (1830) and the rising dominance of physics as a laboratory science.

He intended to make a "scientific tour" of the country and had a goal of using his expertise to accurately map the Mississippi River Valley.

[5] Upon his arrival 1835 in St. Louis, Nicollet gained support for his plan to map the Mississippi River from the American Fur Company and the wealthy Choteau family (who had helped found St. Louis and long had a fur trading monopoly with the Osage tribe based on contracts with former Spanish authorities and later status as U.S. Indian agent).

[3][4] Nicollet departed Fort Snelling by canoe on July 29, 1836, accompanied by Chagobay, an Ojibwe chief, his nine-year-old son, and a half-French guide named Brunia.

[3] Upon his return to Washington, D.C. to report his findings, Nicollet was appointed to head the newly formed Corps of Topographical Engineers and lead a War Department-funded expedition to map the area between the Mississippi and Missouri Rivers in order to correct the western maps affected by Pike's mistake.

[7] In his third and final expedition, guided by Louison Freniere, Nicollet retained the assistance from Frémont and was joined for part of his journey by the Jesuit Missionary Pierre-Jean De Smet.

[7] This journey was also government funded and took Nicollet northwest from Iowa along the Missouri River toward Fort Pierre, South Dakota.

[3][4] He is buried at the Congressional Cemetery, his gravestone noting "He will triumph who understands how to conciliate and combine with the greatest skill the benefits of the past with the demands of the future.

Morever, Nicollet's maps were among the first in the world to depict elevation by hachuring and are among the only sources for original Native American place names in the region.

[3] Many of Nicollet's sketches and journals from his expeditions are housed at the Library of Congress, the Smithsonian Institution, and the National Archives.