The aim of this research was to evaluate the mediating effect of the value orientations of collectivism and individualism on the relationship between ethnic identity and well-being, the latter conceived from the worldview of Andean natives. For this purpose, under an observational and cross-sectional design, 395 Lickan-Antay adults (57% women) living in areas of indigenous development and in two cities in northern Chile were surveyed. We used the Lickan-Antay BLA32 well-being scale, a short version of the Portrait 21 Values Questionnaire to measure individualistic and collectivistic values, and an adapted version of the Ethnic Identity Scale. The results show that ethnic identity had a direct positive effect on all three dimensions of well-being (harmony with community life, ethnic harmony and harmony with nature), and total indirect effects on all five dimensions of well-being, one of them originating mainly from collectivist orientations. Individualistic orientations also showed a positive, though less intense, mediating effect on well-being. We conclude that collectivist and individualistic motivational patterns coexist in Lickan-Antay natives and explain an important part of the relationship between ethnic identity and well-being. Finally, we discuss our results and suggest replication of this study in other ethnic contexts to assess the generalizability of these findings to other native peoples of the Andean region of South America.