In times of resurging racism in many countries all around the globe, xenophobia seems a human universal. However, most civilizations also provide pervasive proof of the opposite phenomenon - xenophilia (“xenos” – “stranger” and philía – “friendship, love”) that manifests itself in multiple and peaceful ways of intercultural exchange in the arts and sciences, international trading, humans’ historic interests in extinct cultures, “new” cultures or travelling. Previous research suggests that xenophile and xenophobic orientations are predicted by distinct sets of personality traits according to the HECACO personality framework (Stürmer et al., 2013, Barbarino & Stürmer, 2016). Xenophile orientations (e.g., favorable attitudes toward immigrants, habitual cross-cultural exploration, and favorable attitudes contact toward indigenous people) are predicted by endeavor-related personality traits (i.e, eXtraversion, Openness, Conscientiousness), whereas xenophobic orientations are predicted by altruism/cooperation-related personality traits (i.e., Honesty-Humility, Emotionality, Agreeableness). While previous research focused primarily on “Westerners”, in the present study we investigated cross-cultural differences and similarities in the pattern of results. A pre-registered online questionnaire study (N = 1455) was conducted in Germany (n = 285), Japan (n = 312), Spain (n = 273), Turkey (n = 191), USA (n = 190) and Mexico/Chile (n = 204). Results suggest that within and across countries, previous findings could be largely replicated: Endeavor-related personality traits explained multiple times of the variance in xenophilia than altruism/ cooperation-related traits, while the reverse was true for the prediction of xenophobia. We further explored psychologically and culturally relevant moderator variables for the relationship between personality traits and xenophile and xenophobic orientations: Relationships were moderated by intergroup threat, but not by collectivistic cultural orientations. Results are discussed in terms of cross-cultural universalities and specificities of xenophilia and xenophobia.