Background and objectives: The incidence of injuries in rugby is extremely high, but studies have rarely examined the predictors of injury in amateur players. This study aimed to systematically analyse sports and injury factors as potential predictors of musculoskeletal injuries in senior-level amateur rugby players. Methods: The participants in this study were 101 senior-level rugby players from Croatia (average of 24.64 years old). At baseline, all participants were tested on sociodemographic and anthropometric parameters (age, body height and mass), consumption of dietary supplements, preseason injury status and training volume, and sport factors (position in game). Data on injury occurrence (dependent variable), prevalence of pain, training status, and characteristics of the played match were surveyed prospectively once a week during the three-month period (one half-season). Results: The logistic regression revealed a higher injury occurrence in forward players of the 1st row, 2nd row (OR = 5.07; 95% CI: 1.64-15.69), and center (OR = 4.72; 95% CI: 1.28-14.31), with reference to outside back players. When observed univariately, higher body mass, higher level of competition, more weekly training sessions, self-perceived pain, and playing with pain were significant injury risk factors. The multivariate logistic regression identified pre-season injury (OR = 1.30, 95% CI: 1.09-1.52), higher level of the game/match (OR = 1.44, 95% CI: 1.13-1.76), higher body mass (OR = 1.03, 95% CI: 1.01-1.05), and pain prevalence (OR = 5.71, 95% CI: 3.22-7.70) as multivariate predictors of injury occurrence over the season. Conclusion: The results of this study showed that among sport factors, the playing position, level of competition, and training exposure represent major injury risk factors. Therefore, in order to reduce the number of injuries, special emphasis should be placed on the specific tackling technique of forward players, which could both increase their situational efficiency and protect them from injuries. Additionally, perceived pain, injury history, and playing with injury were noted among injury factors as the ones that can be predictors of future injuries. In that manner, it is important that coaching and medical staff monitor players with previous injuries and with pain symptoms in order to act preventively against injury occurrence.