Ganoderma tsugae is a typical white-rot fungus capable of decaying both coniferous and broad-leaved trees and is also used in traditional Chinese medicine for its immunomodulatory and anticancer properties. To elucidate the molecular basis of its broad substrate adaptability, we performed integrated genomic and transcriptomic analyses of two G. tsugae strains (collected from Xingjiang on Betula and Jilin on Larix). The high-quality genomes of G. tsugae Wu 2022 from Xinjiang (40.8 Mb, 12,496 genes) and G. tsugae Cui 14110 from Jilin (45.6 Mb, 13,450 genes) were obtained. There are enriched gene families related to carbohydrate-active enzymes (CAZymes) in two G. tsugae strains. Notably, specific CAZyme families implicated in hemicellulose (GH16), chitin metabolism (GH18), and ester bond cleavage (CE10) were prominently expanded. Transcriptome analyses under the induction of Betula and Larix sawdust revealed a core adaptive response. A total of 5558 genes were differentially expressed, including 2094 up-regulated and 3464 down-regulated genes. Most differentially expressed genes (DEGs) were annotated as “catalytic activity”, “metabolic processes” and specific functions such as nutrient transport (“MFS transporter”), and lipid metabolism (“3-oxoacyl-[acyl-carrier protein] reductase”). In addition, a conserved suite of the eleven shared DEGs were annotated as “Heat shock protein 9/12”, “alcohol dehydrogenase”, and “Cytochrome p450” related to secondary metabolites biosynthesis, transport, and catabolism. Based on the annotation results, the wood degradation mechanism of G. tsugae can be described as synthesizing and secreting degradation enzyme system to obtain energy, using protective enzyme systems to ensure its own health, and employing a transport enzyme system to recycle metabolic capacity. This progress ensures the environmental adaptability and high degradation efficiency of G. tsugae during wood degradation.