Gene variants contribute to both physical performance and injury susceptibility in athletes. Given that progression to elite sport requires long-term exposure to high mechanical and physiological loads, while recurrent injuries markedly impair career development, it was hypothesized that injury-resistant gene variants are more frequent in athletesthan in control individuals. A total of 329 elite game-based athletes and 170 controls were genotyped for 13 genetic variants previously associated with injury risk in at least two independent studies (ACTN3 rs1815739, CASP8 rs1045485, COL12A1 rs970547, COL1A1 rs1107946, COL1A1 rs1800012, COL3A1 rs1800255, COL5A1 rs12722, IL6 rs1800795, MIR608 rs4919510, MMP3 rs650108, TIMP2 rs4789932, TNC rs2104772, and VEGFA rs2010963). Genetic associations with athlete status were evaluated individually and collectively, and a Polygenic Score (PGS) based on the candidate variants was constructed and evaluated. Four injury-resistant alleles, ACTN3 rs1815739-C (OR = 1.48, 95% CI: 1.13–1.93), TIMP2 rs4789932-T (OR = 1.39, 95% CI: 1.07–1.82), VEGFA rs2010963-G (OR = 1.34, 95% CI: 0.99–1.82), and COL12A1 rs970547-G (OR = 1.32, CI: 0.95–1.83), were significantly associated with athlete status (P < 0.05), of which ACTN3 rs1815739-C and TIMP2 rs4789932-T remained significant after correction for multiple testing. Finally, the PGS was positively associated with athlete status (AUC–ROC = 0.62; OR = 1.57, P = 2.68×10−6). In conclusion, these findings support the hypothesis that injury resistance, in addition to physical performance, contributes to the attainment of elite status in game-based sports.