The Manila clam (Ruditapes philippinarum) is one of the most important shellfish species cultured in China. The impact of disease on clam culture is becoming increasingly serious due to the deteriorated aquaculture environment. In July 2015, outbreaks of parasitic disease in the Dalu Island area resulted in death of Manila clams in large numbers. In this study, the parasite was morphologically characterized and its 18S rDNA was sequenced. Anatomical analysis of the infected clams showed that the parasites mainly distributed in the gonad tissue and those infected tissues could barely produce sperm or eggs. A BLAST search against the NCBI database using the 18S rDNA sequence showed that the parasite was 92% similar to the trematode Steringophorus margolisi (GenBank sequence AJ287578.1.1934). To investigate the infection mechanisms of this parasite, expression levels of the genes involved in reproductive processes (sodium–glucose transport protein, cytochrome P450 family 1 subfamily A member 1, lambda-crystallin, collagen alpha-1(IV) chain, inhibitor of apoptosis proteins, and 17β-hydroxysteroid dehydrogenases) were examined in infected and uninfected individuals, respectively. This study provides novel and preliminary data on the molecular mechanisms underlying the reproduction failure in digenetic trematode-infected Manila clams.