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Traumatic muscle injuries (TMIs) and muscle pain (MP) negatively impact athletes’ performance and quality of life. Both conditions have a complex pathophysiology involving the interplay between genetic and environmental factors. Yet, the existing data are scarce and controversial. To provide more insights, this study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) previously linked to athletic status with TMI and MP after exercise among Brazilian high-performance athletes from different sports modalities (N = 345). The impact of important environmental determinants was also assessed. From the six evaluated SNPs (<i>ACTN3</i> rs1815739, <i>FAAH</i> rs324420, <i>PPARGC1A</i> rs8192678, <i>ADRB2</i> rs1042713, <i>NOS3</i> rs1799983, and <i>VDR</i> rs731236), none was significantly associated with TMI. Regarding MP after exercise, <i>ACTN3</i> rs1815739 (CC/CT vs. TT; adjusted odds ratio (aOR) = 1.90; 95% confidence interval (95%Cl), 1.01–3.57) and <i>FAAH</i> rs324420 (AA vs. AC/CC; aOR = 2.30; 95%Cl, 1.08–4.91) were independent predictors according to multivariate binomial analyses adjusted for age (≥23 vs. <23 years), sex (male vs. female), and tobacco consumption (yes vs. no). External validation is warranted to assess the predictive value of <i>ACTN3</i> rs1815739 and <i>FAAH</i> rs324420. This could have implications for prophylactic interventions to improve athletes’ quality of life.