The significance of meaningful work for quality of work life has been confirmed by research showing its importance both as regards to employee motivation, well-being, and commitment as well as organizational outcomes such as turnover intentions, citizenship behaviour, and customer satisfaction. In explaining what makes work meaningful, Self-Determination Theory (SDT) provides a potent theoretical framework, linking meaningful work to the satisfaction of human psychological needs. Accordingly, we draw on SDT and research on prosocial behavior to examine what we identify as the four most potential psychological pathways to meaningful work: beneficence and the psychological needs for autonomy, competence, and relatedness. We tested these four antecedents in a three-waves longitudinal design among a large sample of Chilean workers (T1 N = 631, T2 N = 240, T3 N = 148). We found that both autonomy and beneficence prospectively predict subsequent meaningful work above and beyond the other two needs and baseline levels of meaningful work. These results advance theory on key psychological pathways to meaningful work and have important practical implications for how organizations and managers can foster meaningfulness in the workplace through cultivating autonomy and beneficence.