Background: This study aims to determine the injury incidence among male and female athletes in the Turkish Handball Super League and to examine the most common types, mechanisms, and risk factors of injuries. Methods: Data were collected through medical records and self-reported questionnaires from 160 handball Super League players (82 females, 78 males). Injuries were classified based on their type, severity, mechanism (contact vs. non-contact), and affected body region. Statistical analyses were performed using the Mann–Whitney U test to assess differences between groups and logistic regression analysis to evaluate potential predictors of injury, respectively. Results: The findings revealed that lower extremity injuries (54.0%) were the most frequent, followed by upper extremity (27.8%) and trunk injuries (15.1%). Among lower extremity injuries, ankle (22.2%) and knee (15.1%) injuries were the most common, while shoulder injuries (15.9%) were predominant in the upper extremity. Female players exhibited a higher incidence of ACL injuries, whereas Achilles tendon injuries were more prevalent in male players. Logistic regression analysis identified gender (p = 0.041) as a significant predictor of injury risk, while age, BMI, playing position, and years of experience were not statistically significant (p˃ 0.05). Conclusion: The study highlights gender-specific injury trends in elite handball players, emphasizing the need for injury prevention programs focusing on neuromuscular training, load management, and biomechanical assessments. Future research should explore hormonal influences, biomechanical factors, and training adaptations to further reduce injury risk. These findings serve as a valuable guide for coaches, medical teams, and sports scientists in optimizing handball injury prevention strategies.