Existing research on Big Five personality and unemployment has relied on personality measures elicited after the respondents had already spent years in the labor market, an experience that could change personality. We clarify the direction of influence by using the British Cohort Study (N = 4,206) to examine whether conscientiousness and other Big Five personality traits at age 16–17 predict unemployment over age 16–42. Our hypothesis that higher conscientiousness in adolescence would predict lower unemployment was supported. In analyses controlling for intelligence, gender, and parental socioeconomic status, the less conscientious (−1 SD) had a predicted probability of unemployment twice as high (3.4% vs. 1.7%) as the highly conscientious (+1 SD), an effect size comparable to intelligence. Mediation analysis revealed that academic motivation and educational attainment explained only 8.9% of this association. Fostering conscientiousness in early life may be an effective way to reduce unemployment throughout adulthood.