Popcorn disease is an important disease of mulberries (Fructus mori) due to invasion of Ciboria carunculoides, and losses are common in Chinese growing regions. This study was to investigate the process of pathogenic invasion, the pathological changes of cellular tissues of mulberry fruits and seeds, and resistance of seeds at different maturity levels using optical microscopes in combination with an electron microscope for observation. The results indicated 72.90% ascospore and hyphae adhered to female stigma with an ascosporic germination rate at 77.80%. After 10 days of hyphae inoculation, their invasion extended to the ovary, inner and outer perianths and interior of young seeds via stigmatic intercellular spaces. After 15 days, numerous filamentous haustoriums were generated with gradually complete disappearance of the host cell structure. In the following 20 to 30 days, few hyphae and numerous spherical haustoriums generated young sclerotium in mulberry fruit leading to the form of popcorn with the grey-white colour appearance of dying feature. The morbidity of mulberry fruits was at 96.53%. Embryo and endosperm of the mature seed coated by sclerotium showed normal cell morphology and that the plant heights of the seedling grown from the infected seeds showed no significant variations (p > 0.05) in comparison with the healthy seeds’ seedling. Consequently, understanding that mulberry female flower stigma becoming the foremost invaded part avails the development of prevention and control against mulberry sclerotinose. Additionally, that mature seeds possessed excellent resistance to sclerotinose was highly possible due to compactness and the secondary metabolites with antibacterial activities in the seed coat. Moreover, there are uncertainty about the attachment of ascospores and stromatic ascospores.