The present study aimed to examine the role of acculturation in mitigating the negative impact of perceived stress on depressive symptoms among U.S. Chinese older adults. Data of 3,159 Chinese adults over 60 years old were drawn from the Population Study of Chinese Elderly in Chicago (PINE). In addition to socio-demographic variables, participants' acculturation levels, perceived stress, and depressive symptoms were assessed. Perceived stress was positively related to depressive symptoms among Chinese older adults. However, no significant association was found between acculturation level and depressive symptoms. Regression analysis supported the moderation hypothesis of acculturation level on the relationship between perceived stress on depressive symptoms. The negative impact of perceived stress on depressive symptoms was mitigated for Chinese older adults who had higher levels of acculturation than for those who had lower levels of acculturation. The findings have implications in minority aging and mental health policies during the on-going pandemic era.