Though he never rose above the rank of private in his three years of service, Greene was able to advance his botanical studies, collecting specimens as he marched through Tennessee, Kentucky and Alabama.

With the aid of botanists Asa Gray of Cambridge, Massachusetts and George Engelmann of St. Louis, Missouri, Greene made preparations to study botany in the West.

In 1876–1877, while Greene was an episcopal priest in Yreka, California, he discovered the first specimens of Phlox hirsuta, a small flowering plant found only in that area.

Between his arrival in 1881 and 1883, Greene began to drift away from the Episcopal Church toward Roman Catholicism, costing him his congregation and his standing within the ministry.

Greene returned to Washington, D.C., in October that same year to continue work on the Landmarks of Botanical History, Part 2, which would eventually be published posthumously in 1983.

By the end of his career Greene had named over 4,400 new species of plants, published 565 original papers, and amassed a library of over 4,000 volumes, some of which have no duplicates in North America.