Handball is a sport that involves high-intensity actions throughout the game, such as sprints, jumps, landings, and high-speed, repeated throws. This, along with competitive and tactical factors, congested schedules, and the need to maintain a high level of performance throughout the season, contributes to a high injury rate. This study aimed to analyse ligament injuries in a professional handball team over six consecutive seasons. A total of 68 elite male Spanish handball players participated, with 54 time-loss injuries (i.e., injuries involving at least one day of absence) observed during this study period. Ligament injury information was recorded following the International Olympic Committee consensus statement. The overall incidence was 0.89 ligament injuries per 1000 h of exposure. Additionally, a higher incidence and burden of ligament injuries was observed during match-play compared to training. Most ligament injuries were classified as minor or moderate (i.e., 79.63% of the total), and 46.29% were reinjuries. A significantly higher incidence of ligament injuries was suffered in the lower limbs compared to the upper limbs (0.81 vs. 0.08 ligament injuries per 1000 h; < 0.001). Specifically, the highest incidence was observed in the anterior talofibular ligament of the ankle (0.57 injuries per 1000 h of exposure), while the greatest burden was related to the anterior cruciate ligament (24.08 absence days per 1000 h of exposure). This study provides an overview of ligament injuries among professional handball players, highlighting the need to implement strategies with positive effects during competition (e.g., specific activation strategies or training programmes based on strength and balance) and to reduce injury recurrences.