East Asians and Asian-Americans tend to allocate relatively greater attention to background context compared to European Americans across a variety of cognitive and neural measures. We sought to extend these findings of cultural differences to affective stimuli using the N400, which has been shown to be sensitive to deep processing of affective information. The degree to which Asian-Americans and European Americans responded to semantic incongruity between emotionally expressive faces (i.e., smiling or frowning) and background affective scenes was measured. As predicted, Asian-Americans showed a greater N400 to incongruent trials than to congruent trials. In contrast, European Americans showed no difference in amplitude across the two conditions. Furthermore, greater affective N400 incongruity was associated with higher interdependent self-construals. These data suggest that Asian-Americans and those with interdependent self-construals process the relationship between perceived facial emotion and affective background context to a greater degree than European Americans and those with independent self-construals. Implications for neural and cognitive differences in everyday social interactions, and cultural differences in analytic and holistic thinking are discussed.