James is primarily remembered for his participation in the expedition of 1820 led by Major Stephen Harriman Long, into still largely unknown territory acquired in the Louisiana Purchase.

"[1] James was primarily responsible for producing the report, Account of an Expedition from Pittsburgh to the Rocky Mountains, Performed in the Years 1819, 1820, published in 1823.

The expedition's extensive collection of information on flora, fauna, geology and geography, as recounted in James' Account, is reminiscent of the efforts, just two decades earlier, by Alexander von Humboldt in Central and South America.

"[4][5] In a more recent homage to James, Lyndgaard said: "The passages that deal with landscape description, bison, and Native Americans, especially the Pawnee, were immediately recognized for their quality, and were thus mined by novelists as well as celebrated by reviewers.

[9] The second year of the Long Expedition began June 6, 1820 when the members, now including 22-year-old Edwin James, left the overwintering camp, Engineer Cantonment, near the eastern border of the current state of Nebraska.

As James writes in his Account: On the morning of the 14th... we continued the ascent, hoping to be able to reach the summit of the Peak, and return to the same camp in the evening... A little above the point where the timber disappears entirely, commences a region of astonishing beauty... covered with a carpet of low but brilliantly flowering alpine plants... We now found it would be impossible to reach the summit of the mountain, and return to our camp of the preceding night, during that part of the day which remained; but as we could not persuade ourselves to turn back, after having so nearly accomplished the ascent, we resolved to take our chance of spending the night, on whatever part of the mountain, it might overtake us... We met, as we proceeded, such numbers of unknown and interesting plants, as to occasion much delay in collecting, and were under the disagreeable necessity of passing by numbers which we saw in situations difficult of access.

[2]Historian Roger Lawrence Williams[11] used the phrase "a region of astonishing beauty", from the above, for the title of his 2003 book on Rocky Mountains botanical history.

[10] In addition to Aquilegia coerulea, James named many other species (e.g., Limber Pine, Pinus flexilis E.James), and many were later named after him by John Torrey (notably the Cliffbush, Jamesia americana Torr & A.Gray, often found at high elevations growing in cracks in vertical rock surfaces), and by others who worked on his collections (e.g., Telesonix jamesii (Torr.)

[10] In his 1920 100 year anniversary commemoration, Osterhout noted: "In general the native plants still grow and blossom as they did when Dr. James saw them in 1820; but a great change has been wrought in the country.

Fruitful farms have replaced much of what seemed to be sterile soil, and towns and cities and a busy industry have come to their silent and uninhabited plains and hills.

James was assigned the primary responsibility (with collaboration by Long and Say) of writing the Account 's narrative, to append the collected data, and to prepare the results for publication, a job completed near the end of 1822.

[14] In 1827, while still working for the Army but during a return visit to the East, James married Clara Rogers, who was describes as a beautiful woman "of talent and fond of society".

Two bounty hunters from Missouri, a slave state, came to town in search of a man named Dick who escaped from a farm in Clark County.

Years later, Rocky Mountain Blue Columbine were planted around his grave by the Des Moines County Medical Society.