Running participation has increased significantly in the last decade. Despite its association with different health-related aspects, athletes may experience adverse outcomes, including injuries. The aim of this study was twofold: to examine the relationship between runners' resilience levels, motivation and incidence of injury, on the one hand; and to analyse the mediation that intrinsic and extrinsic motivation has on the association between the number of injuries and psychological resilience levels among amateur athletes. The sample consisted of a total of 1725 runners (age: 40.40 ± 9.39 years), 1261 of whom were male (age: 43.16 ± 9.38), and 465 of whom were female (age: 40.34 ± 9.14). Athletes completed the Behavioural Regulation in Exercise Questionnaire (BREQ-3), the Resilience scale (CD-RISC 10), and an Injury retrospective survey. Three mediation models were constructed, and the results showed a significant indirect association of athletes' intrinsic motivation and resilience on the number of injuries (β = 0.022, CI = 0.007, 0.0) in mediation model 1, whereas extrinsic motivation was found to have no significant association on those variables (β = -0.062, CI = -0.137, 0.009) in mediation model 2. Model 3 showed significant differences with respect to resilience (p < 0.05) and intrinsic motivation (p < 0.05). Therefore, the mediation of intrinsic motivation on athletes' resilience levels and incidence of injury was demonstrated, i.e., it was found that intrinsic motivation was associated with a higher incidence of injury, while no such correlation was found for extrinsic motivation. This study shows that the amateur long distance runners with a high level of intrinsic motivation tend to suffer from a greater number of injuries, and at the same time psychological resilience was associated with a lower number of injuries.