The extents and mechanisms of mental health stigma varies intensely between the eastern culture and the western culture, while empirical insights are scarce. Also, stigma on schizophrenia is more intense than which on other forms of mental disorders. The present experiment examined cultural differences on stigma toward schizophrenia among Chinese and Americans (N = 184), with a pivotal focus on whether a knowledge intervention would alleviate stigma controlling for face concerns. No significant cultural differences were found in the mean levels when knowledge interventions were absent, while the Chinese participants reported lower levels of stigma than Americans with the interventions present. In addition, the strengths of paths from knowledge intervention to stigma was significant controlling for face concerns. These findings empirically revealed the mean level and underlying mechanisms of cultural differences in mental health stigma and went beyond to unpackage the observed differences by testing the mediating role of different cultural values. Some underlying mechanisms were more significant than others. We discussed theoretical and practical implications of the findings in the discussion.