Naematelia aurantialba is a rare edible fungus with both nutritional and medicinal values and especially rich in bioactive polysaccharides. However, due to the lack of genomic information, researches on the mining of active compounds, artificial breeding and cultivation, genetics, and molecular biology are limited. To facilitate the medicinal and food applications of N. aurantialba, we sequenced and analyzed the whole genome of N. aurantialba for the first time. The 21-Mb genome contained 15 contigs, and a total of 5860 protein-coding genes were predicted. The genome sequence shows that 296 genes are related to polysaccharide synthesis, including 15 genes related to nucleoside-activated sugar synthesis and 11 genes related to glucan synthesis. The genome also contains genes and gene clusters for the synthesis of other active substances, including terpenoids, unsaturated fatty acids, and bioactive proteins. In addition, it was also found that N. aurantialba was more closely related to Naematelia encephala than to Tremella fuciformis. In short, this study provides a reference for molecular cognition of N. aurantialba and related researches.