The wear behavior and mechanisms of a Cr-Mo-V cast hot-working die steel with three microstructures (tempered martensite, troostite, and sorbite) were studied systematically through the dry-sliding wear tests within a normal load range of 50 to 300 N and an ambient temperature range of 298 K to 673 K (25°C to 400°C) by a pin-on-disk high-temperature wear machine. Five different mechanisms were observed in the experiments, namely adhesive, abrasive, mild oxidative, oxidative, and extrusive wear; one or more of those mechanisms would be dominant within particular ranges of load and temperature. The transition of wear mechanisms depended on the formation of tribo-oxides, which was related closely to load and temperature, and their delamination, which was mainly influenced by the matrix. By increasing the load and ambient temperature, the protective effect of tribo-oxides first strengthened, then decreased, and in some cases disappeared. Under a load ranging 50 to 300 N at 298 K (25°C) and a load of 50 N at 473 K (200°C), adhesive wear was the dominant wear mechanism, and abrasive wear appeared simultaneously. The wear was of mild oxidative type under a load ranging 100 to 300 N at 473 K (200°C) and a load ranging 50 to 150 N at 673 K (400°C) for tempered martensite and tempered troostite as well as under a load of 100 N at 473 K (200°C) and a load ranging 50 to 100 N at 673 K (400°C) for tempered sorbite. At the load of 200 N or greater, or the temperatures above 673 K (400°C), oxidative wear (beyond mild oxidative wear) prevailed. When the highest load of 300 N at 673 K (400°C) was applied, extrusive wear started to dominate for the tempered sorbite.