Agility is an important factor in football (soccer), but studies have rarely examined the influences of different agility components on the likelihood of being injured in football. This study aimed to prospectively evaluate the possible influences of sporting factors, i.e., flexibility, reactive agility (RAG), and change of direction speed (CODS), on injury occurrence over one competitive half-season, in professional football players. Participants were 129 football professional players (all males, 24.4 ± 4.7 years), who underwent anthropometrics, flexibility, and RAG and CODS (both evaluated on non-dominant and dominant side) at the beginning of second half-season 2019/20 (predictors). Over the following half-season, occurrence of injury was registered (outcome). To identify the differences between groups based on injury occurrence, t-test was used. Univariate and multivariate logistic regressions were calculated to identify the associations between predictors and outcome. Results showed incidence of 1.3 injuries per 1000 hours of training/game per player, with higher likelihood for injury occurrence during game than during training (Odds Ratio (OR) = 3.1, 95%CI: 1.63–5.88) Univariate logistic regression showed significant associations between players’ age (OR = 1.65, 95%CI: 1.25–2.22), playing time (OR = 2.01, 95%CI: 1.560–2.58), and RAG (OR = 1.21, 95%CI: 1.09–1.35, and OR = 1.18, 95%CI: 1.04–1.33 for RAG on dominant- and non-dominant side, respectively), and injury occurrence. The multivariate logistic regression model identified higher risk for injury in those players with longer playing times (OR = 1.81, 95%CI: 1.55–2.11), and poorer results for RAG for the non-dominant side (OR = 1.15, 95%CI: 1.02–1.28). To target those players who are more at risk of injury, special attention should be paid to players who are more involved in games, and those who with poorer RAG. Development of RAG on the non-dominant side should be beneficial for reducing the risk of injury in this sport.