He is considered a founding father of plant pathology (phytopathology) as well as the founder of modern mycology. His extensive and careful studies of the life history of fungi and contribution to the understanding of algae and higher plants were landmarks of biology.
After the graduation, de Bary practiced medicine in Frankfurt, but only for a very short period of time. He was drawn back to botany and became Privatdozent in botany at the University of Tübingen, where he worked as an assistant to Dr. Hugo von Mohl (1805–1872) for a while. In 1855, he succeeded the position of the well-known botanist Karl Wilhelm von Nägeli (1818–1891) at Freiburg, where he established the most advanced botanical laboratory at the time and directed many students.
De Bary married Antoni Einery in 1861; they raised four children. In 1867, de Bary moved to the University of Halle to succeed the position of Professor Diederich Franz Leonhard von Schlechtendal, who, with Hugo von Mohl, co-founded the pioneer botanical journal Botanische Zeitung. De Bary became the co-editor and later the sole editor of this journal. As an editor and a contributor of this journal, he exercised a great influence upon the development of botany. After the Franco-Prussian war (1870–1871), de Bary was appointed professor of botany at the University of Strasbourg, founder of the Jardin botanique de l'Université de Strasbourg, and also elected to the first rector (president) of the reorganized university. He conducted many research in the university botanical institute and attracted many students from Europe and America, and made a great contribution to the development of botany.
De Bary was devoted to the study of the life history of fungi. At that time, various fungi were still considered to arise through spontaneous generation. He proved that pathogenic fungi were not the products of cell contents of the affected plants, and they did not arise from the secretion of the sick cells.
In de Bary’s time, potato blight had caused sweeping crop devastation and economic loss. He studied the pathogen Peronospora infestans and made a great contribution by elucidating its life cycle. The origin of plant diseases was not known at that time. Much as Miles Joseph Berkeley (1803–1889) had insisted in 1841 that the fungus found in potato blight was the cause of diseases, de Bary declared that the rust and smut fungi were the causes of the pathological changes in disease plants. He concluded that Uredinales and Ustilaginales were parasites.
De Bary spent a considerable amount of time studying the morphology of fungi and noticed that certain forms, which had been classified as separate species, were actually successive stages of development of the same organism. De Bary studied the developmental history of Myxomycetes (slime molds), and thought it was necessary to reclassify the lower animals. He first coined the term Mycetozoa to include lower animals and slime molds. In his work on Myxomycetes (1858), he pointed out that at one stage of their life cycle (the plasmodial stage), they were little more than formless, motile masses of the substance, that Félix Dujardin (1801–1860) had called sarcode (protoplasm). This is the fundamental basis of the protoplasmic theory of life.
De Bary was the first to demonstrate sexuality in fungi. In 1858, he had observed conjugation in the alga Spirogyra, and in 1861, he described sexual reproduction in the fungus Peronospora sp. He saw the necessity of observing the whole life cycle of pathogens and he attempted to follow it in the living plants.
De Bary published his first work on fungi in 1861, then, he spent more than 15 years studying Peronosporeae, particularly the Peronospora infestans and Cystopus (Albugo), parasites of potatoes. In his published work in 1863 entitled "Recherches sur le developpement de quelques champignons parasites", he inoculated spores of P. infestans on health potato leaves and observed the penetration of the leaf and the subsequent growth of the mycelium that affected the tissue, the formation of conidia and the appearance of the characteristic black spots of the potato blight. He also did similar experiments on potato stalks and tubers. He watched conidia in the soil and their infection of the tubers. He observed that mycelium could survive the cold winter in the tubers. From all these studies, he concluded that organisms could not be generated spontaneously.
He did a thorough investigation on Puccinia graminis, the pathogen of rust of wheat, rye and other grains. He noticed that P. graminis produced reddish summer spores called "urediospore", and dark winter spores called "teleutospores". He inoculated sporidia from the winter spores of the wheat rust on the leaves of the "common barberry" (Berberiso vulgaris). The sporidia germinated and led to the formation of aecia with yellow spores—that was the familiar symptoms of infection on the barberry. De Bary then inoculated aecidiospores on moisture-retaining slides, then inoculated these to the leaves of seedling of rye plants. In time, he observed the reddish summer spores appeared in the leaves. The sporidia from the winter spores germinated, but only on barberry. De Bary clearly demonstrated that P. graminis required different hosts during the different stages of its development (a phenomenon he called "heteroecism" in contrast to "autoecism", when development take place only in one host). De Bary’s discovery explained why the eradication of the barberry plants had long been practiced as a control for rust.
De Bary also studied the formation of lichens which are the result of an association between a fungus and an alga. He traced the stages through which they grew and reproduced and the adaptations that enabled them to survive drought and winter. He coined the word "symbiosis" in 1879 in his monograph "Die Erscheinung der Symbios" (Strasbourg, 1879) as "the living together of unlike organisms". He carefully studied the morphology of molds, yeasts, and fungi and he basically established mycology as an independent science.
De Bary's concept and methods had a great impact on the growing field of bacteriology and botany. He published more than 100 research papers and influenced many students who were later became distinguished botanists and microbiologists such as Sergei Winogradsky (1856–1953), William Gilson Farlow (1844–1919), and Pierre-Marie-Alexis Millardet (1838–1902). He was one of the most influential of the 19th century bioscientists. He died of a tumor of the jaw having submitted to extensive surgery on January 19, 1888 in Strassburg.