The Chinese mitten crab, Eriocheir sinensis, is an important farmed crustacean species in China, outranking other farmed crabs in yield and economic importance. An infection called “milky disease”, caused by the yeast, Metschnikowia bicuspidata, has emerged in E. sinensis farms in northeast China and has caused progressive economic losses. The diseased crabs present with opaque, whitish muscles and milky hemolymph. Currently, there are no effective drugs to treat the infection. Clarifying the transmission route of M. bicuspidata would help to treat and prevent the disease. We investigated the effects of three different M. bicuspidata infection methods (feeding, immersion, and cohabitation) on E. sinensis. All three infection methods led to a high infection rate in healthy crabs. After 35 d, the infection rate was 76.7%, 66.7%, and 53.3% in the feeding, immersion, and cohabitation groups, respectively. Diseased crabs exhibited the typical symptom of hemolymph emulsification, with a high pathogen load of M. bicuspidata. The yeast was not detected in the oocytes of infected crabs. Fertilized embryos, zoea larvae, and megalopae of infected ovigerous crabs tested negative for yeast, indicating that direct transmission from mother to offspring does not occur. Our results highlight avenues for the prevention and control of this yeast.