He was appointed Chief Botanist at the United States Department of Agriculture in 1872, a position he held for the remainder of his life.

In 1854, Vasey opened a dry goods store to support his growing family, which now included four children and his mother, Jane Frankish.

The explorer John Wesley Powell invited George Vasey to participate in an expedition to the Colorado Territory in 1868.

Vasey accepted Powell's offer as Botanist of the Colorado Exploring Expedition of 1868, which left Chicago for Denver in June of that year.

By the time the expedition had reached Cheyenne on July 3rd, Vasey and his companions had already collected one hundred and fifty species.

George Vasey co-edited the journal The American Entomologist and Botanist prior to becoming curator of the Illinois State University Natural History Museum in 1870.

[8] He quickly began work to improve the poor state of the National Herbarium, by organizing an exhibit of the country's trees for the Centennial Exposition in Philadelphia.

The herbarium, hosted by the Smithsonian Institution, is considered the crowning achievement of his career, particularly its grass collection, of which he was a specialist.

With George Thurber he worked on grasses for Asa Gray and John Torrey's Flora of North America.

The expedition covered the region from the mouth of the Clearwater River near Lewiston northward to Lake Pend Oreille in the northern Idaho Panhandle.

Among the plant collectors on the expedition were Amos Arthur Heller, John Herman Sandberg, and Daniel Trembly MacDougal.

[10] In July, the party met the plant collector John Bernhard Leiberg at Lake Pend Oreille.

Upon his death in 1893, a comprehensive bibliography of the published works by George Vasey was prepared by Josephine A. Clark, Botanical Division, U.S. Department of Agriculture.

[13] In addition, there are dozens of published botanical names that include an epithet such as vaseyi, vaseyanus, vaseyana, or vaseyanum.

[19] At a time when Vasey was still practicing medicine in Illinois, Thurber characterized him as "one of the most zealous of our Western botanists".

Engelmann described Vasey as a man "who paid a good deal of attention to [Juncus] and to the botany of his neighborhood generally".