Calcarisporium cordycipiticola is a mycoparasite of the edible fungus Cordyceps militaris, and mycoparasitism causes devastating diseases of mushrooms. In this study, dual-transcriptomic analysis was performed to reveal interspecific interactions between the mycoparasite C. cordycipiticola and its host C. militaris. At 4 and 8 days postinfection (dpi), 2,959 and 2,077 differentially expressed genes (DEGs) of C. cordycipiticola and 914 and 1,548 DEGs of C. militaris were identified compared with the mycelial stage, respectively, indicating that C. cordycipiticola responded more quickly than C. militaris. Lectins of the pathogen may play a role in the recognition of fungal prey. Both Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that primary metabolism was vigorous for the pathogen to colonize the host and that the pathogen's attack substantially altered C. militaris' primary metabolism. C. cordycipiticola upregulated some carbohydrate-active enzyme (CAZyme) genes, including CBM18, GH18, GH16, and GH76, for degrading the host cell wall and defending against host immunity. C. militaris produced excessive reactive oxygen species (ROS) to respond to the infection. The GO term "heme binding" was the only shared term enriched at both stages at 4 and 8 dpi, indicating that iron was important for both the pathogen and the host. The uptake of iron by pathogens through multiple pathways promoted colonization and removed high ROS levels produced by the host. The transcription levels of Cmhsp78, Cmhsp70, and Cmhyd1 in C. militaris responded quickly, and these genes have potential as candidates for the breeding of resistant varieties. This study provides clues for understanding the interactions between a mycoparasite and its mushroom host and will be helpful for the breeding of resistant varieties and disease prevention and control for this edible fungus. IMPORTANCE White mildew disease caused by Calcarisporium cordycipiticola is devastating for the fruiting body cultivation of Cordyceps militaris, a popular and highly valued edible fungus. Here, the pathogenic mechanisms of C. cordycipiticola, the responses of C. militaris to the infection, and the interaction of these two phylogenetically close species were revealed by time course dual-transcriptome profiles. In general, the host C. militaris responds more slowly than the pathogen C. cordycipiticola. For the first time, we found that iron was important for both the mycoparasite and the host. C. cordycipiticola takes up iron by multiple pathways to promote colonization and remove high ROS levels produced by the host. The rapidly responding genes Cmhsp70, Cmhsp78, and Cmhyd1 in C. militaris may have the potential as candidate genes for the breeding of resistant varieties. This study expands our understanding of the mycoparasitic interactions of two species from sister families and will be helpful for the breeding of and disease prevention and control in mushrooms.