In the current study, we report the high-quality draft genome sequence of Neonectria sp. DH2, an endophytic fungus isolated from Meconopsis grandis Prain in Tibet. The whole genome is about 45.8 Mbp, with a GC content of 53%. A total of 14,163 genes are predicted to encode proteins, and 557 of them are considered as unique, as no matches are found in five gene databases. A neighbor-joining phylogenetic tree based on internal transcribed spacer (ITS) region sequences shows that Neonectria sp. DH2 was most closely related to Neonectria ramulariae. 47 biosynthetic gene clusters (BGC) were identified in Neonectria sp. DH2 genome, and only 5 BGCs shows significant similarities to previously reported BGCs. The presence of 42 unique BGCs in Neonectria sp. DH2 suggests that it has great potential to produce novel secondary metabolites.