This study examined the associations between two types of self-construals (i.e., independent and interdependent), self-esteem, sympathy, and psychological well-being in the United States and Japan. A model was proposed to systematically examine the abovementioned factors among two groups: 1,255 American participants in the 2006 Survey of Midlife in the US and 1,027 Japanese participants in the 2008 Survey of Midlife in Japan. This study found that independent self-construal positively affected self-esteem which leads to psychological well-being, and interdependent self-construal positively influenced sympathy, which in turn had a positive impact on psychological well-being. Moreover, there was a stronger link between sympathy and psychological well-being in the Japanese group than in the American group. There was an also stronger link between interdependent self-construal and sympathy in the Japanese group than in the American group. The results of this study provide new insights into self-construal and the differential impacts of psychosocial antecedents across cultures. Discussion of these findings and their implications is provided.