Phytophthora cactorum is a homothallic oomycete pathogen, which has a wide host range and high capability to adapt to host defense compounds and fungicides. Here we report the 121.5 Mb genome assembly of the P. cactorum using the third-generation single-molecule real-time (SMRT) sequencing technology. It is the second largest genome sequenced so far in the Phytophthora genera, which contains 27,981 protein-coding genes. Comparison with other Phytophthora genomes showed that P. cactorum had a closer relationship with P. parasitica, P. infestans and P. capsici. P. cactorum has similar gene families in the secondary metabolism and pathogenicity-related effector proteins compared with other oomycete species, but specific gene families associated with detoxification enzymes and carbohydrate-active enzymes (CAZymes) underwent expansion in P. cactorum. P. cactorum had a higher utilization and detoxification ability against ginsenosides-a group of defense compounds from Panax notoginseng-compared with the narrow host pathogen P. sojae. The elevated expression levels of detoxification enzymes and hydrolase activity-associated genes after exposure to ginsenosides further supported that the high detoxification and utilization ability of P. cactorum play a crucial role in the rapid adaptability of the pathogen to host plant defense compounds and fungicides.