The pathogenic fungus Cryphonectria parasitica (formerly Endothia parasitica) is a member of the Ascomycota (sac fungi). This necrotrophic fungus is native to East Asia and South East Asia and was introduced into Europe and North America in the early 1900s. Strains of the fungus spread more or less rapidly and caused significant tree loss in both regions. Strains of the fungus can be more or less virulent.

Cryphonectria parasitica is a parasitic fungus of chestnut trees. This disease came to be known as chestnut blight. Naturally found in Southeast Asia, accidental introductions led to invasive populations of C. parasitica in North America and Europe. In the first half of the 20th century, the fungal disease had a devastating economic and social impact on communities in the eastern United States. It killed an estimated four billion trees; or, by another count, 3.5 billion trees through 2013. Less severe impacts have occurred in Europe due to widespread CHV1-induced hypovirulence. CHV1 is one of at least two viral pathogens that weaken the fungus through hypovirulence and helps trees survive a blight infection.

The American chestnut (Castanea dentata) and American chinquapin (Castanea pumila) are highly susceptible to chestnut blight. The European chestnut (Castanea sativa) is also susceptible, but due to widespread CHV1 hypovirulence, blight-induced tree death is less common. The fungus can infect other tree species such as oaks, red maples, staghorn sumacs, and shagbark hickories. Once infected, these trees' bark also exhibit orange cankers but may not die. The pathogen can persist in these trees, producing spores that may infect other trees.

Fungal strains spread by wind-borne ascospores and, over a shorter distance, conidia distributed by rain-splash action. Infection can be local in range, so some isolated American chestnuts survive where there is no other infected tree within 10 km (6.2 mi). Soil organisms at the root collar and root system of the chestnut tree are antagonistic to the fungus. Chestnut tree roots are resistant to blight infections. Consequently, a large number of small American chestnut trees still exist as shoots growing from existing root bases. However, these regrown shoots seldom reach the reproductive stage before above ground growth is again girdled by the fungus. Fungal strains originally infected the Chinese chestnut (Ca. mollissima) and the Japanese chestnut (Ca. crenata). These two species have co-evolved with the pathogen, making them most variably resistant to its ill effects.

In 1904, the chestnut blight was accidentally introduced to North America by Robert Fortune. Cryphonectria parasitica was introduced into the United States from East Asia via import of Japanese chestnut trees. Commercial breeding purposes motivated these imports. Infection of American chestnut trees with C. parasitica simultaneously appeared in numerous places on the East Coast, most likely from Japanese chestnuts, which had become popular imports.

Herman W. Merkel, a forester at the New York Zoological Garden (Bronx Zoo) first found infected chestnut trees on the grounds of the zoo. In 1905, American mycologist William Murrill isolated and described the fungus responsible (which he named Diaporthe parasitica), and demonstrated by inoculation into healthy plants that the fungus caused the disease. By 1940, most mature American chestnut trees had been girdled by the disease. It took about 40 years to devastate the nearly four-billion-strong American chestnut population in North America. Today, uninfected wild American chestnut trees are extraordinarily rare, with researchers encouraging members of the public to report sightings. The world's largest remaining stand of genetically pure, mature American chestnut trees is near West Salem, Wisconsin, where scientists have been trying for decades to save the trees while studying the efficacy of hypoviruses that target the blight fungus. Other sightings of mature American chestnut trees have been reported within and outside of its original range, including in Alabama, Kentucky, Maine, Michigan, Ohio, Tennessee, and Vermont.

Japanese and Chinese chestnut trees may resist an infection from C. parasitica. Because of the disease, American chestnut wood almost disappeared from the market for decades, although it can still be obtained as reclaimed lumber.

It is estimated that in some places, such as the Appalachian Mountains, one in every four hardwoods was an American chestnut. Mature trees often grew straight and branch-free for 50 feet and could grow up to 100 feet tall with a trunk diameter of 4–5 feet at a few feet above ground level. The reddish-brown wood was lightweight, soft, easy to split, very resistant to decay, and did not warp or shrink. For three centuries many barns and homes near the Appalachian Mountains were made from American chestnut. Its straight-grained wood was ideal for building furniture and caskets. The bark and wood were rich in tannic acid, which provided tannins for use in the tanning of leather.