He was born at Milton, Wayne County, Ohio. He graduated in 1869 at the Michigan Agricultural College. Bessey also studied at Harvard University under Asa Gray, in 1872 and in 1875–76. He was professor of botany at the Iowa Agricultural College from 1870 to 1884. In 1884, he was appointed professor of botany at the University of Nebraska and became head dean there in 1909. He also served as Chancellor of the University of Nebraska from 1888 to 1891 and again from 1899 to 1900. He served as president of the American Association for the Advancement of Science in 1911.
- The Geography of Iowa (Cincinnati, 1878)
- Botany for High Schools and Colleges (New York, 1880)
- revision of McNab's Botany (1881)
- The Essentials of Botany (1884)
- Elementary Botany (1904)
- Plant Migration Studies (1905)
- Synopsis of Plant Phyla (1907)
- Outlines of Plant Phyla (1909)
- written with others, New Elementary Agriculture (ninth edition, 1911)
His arrangement of flowering plants taxa, with focus on the evolutionary divergence of primitive forms, is considered by many as the system most likely to form the basis of a modern, comprehensive taxonomy of the plant kingdom.
In 2009 he was inducted to the Nebraska Hall of Fame.
Bessey's son, Ernst Bessey was Professor of Mycology and Botany at Michigan State University.
- Bessey system, his taxonomic plant system.
- Nebraska National Forest