Self-reports on the HEXACO-PI-R scales were examined in relation to academic majors in post-secondary education ( N > 73,000). Openness to Experience showed the largest mean differences across academic major areas, with the Visual/Performing Arts and Humanities areas averaging higher and Health Sciences and Business/Commerce averaging lower. Emotionality showed the second largest differences, with the Engineering and Physical Sciences/Math areas averaging lower and Visual/Performing Arts averaging higher; these differences in Emotionality became smaller in within-sex analyses. In addition, Extraversion tended to be higher for Business/Commerce and lower for Physical Sciences/Math, while Honesty-Humility was lower for Business/Commerce. The facet-level analyses provided additional detail, as facet scales in the same domain sometimes showed considerably different means within a given academic major area. In one case, Visual/Performing Art majors averaged lower in Prudence, but higher in Perfectionism, even though both facets belong to the Conscientiousness domain.