College is a stressful time for many students, including student-athletes, who may benefit from mindfulness interventions focusing on present-moment awareness and nonjudgmental acceptance. Mindful sport performance enhancement (MSPE) has shown promise in previous open trials for promoting both athlete well-being and psychological factors related to sport performance, and this first randomized controlled trial of MSPE was conducted with mixed-sport groups of 52 NCAA Division III student-athletes. Each of the six sessions included educational, discussion-based, experiential, and home practice components, with meditation exercises progressing from sedentary mindfulness to mindfulness in motion. Whereas wait-list controls showed significant increases in depressive symptoms, those who received MSPE evidenced non-significant reductions in depressive symptoms over the course of treatment. Furthermore, once controls had also received MSPE, treatment completers (the 41% who attended at least five of six MSPE sessions) demonstrated significant increases in flow, trait mindfulness, satisfaction with life, and self-rated sport performance, along with reductions in worry, with medium to large effect sizes. There were no significant changes for treatment completers from post-treatment to 6-month follow-up, suggesting that improvements were maintained over time.