Purpose: To examine trends in the incidence of pectoralis major (PM) injuries over the last 22 National Football League (NFL) seasons and identify risk factors for injuries requiring operative management. Methods: Publicly available data from the 1998-1999 through 2019-2020 NFL seasons were reviewed to identify PM injuries, demographics, injury mechanisms, and management. Injury incidence was calculated using linear regression per 10,000 athlete-exposures, while risk factors for operative management were identified through multivariate logistic regression. Results: There were 258 PM injuries. Mean athlete age at the time of injury was 27.1 years (range: 21-37) with a mean body mass index of 32.6 (range: 24.8-43.1). Overall incidence was 0.603 per 10,000 athlete-exposures, which was found to significantly increase with time by 0.039 per athlete-exposures per year (R2 = .787, P < .001). Defensive athletes accounted for 64.7% of PM injuries. Repair was performed in 48.8% of athletes, with defensive linemen (odds ratio [OR] 3.78, CI 1.42-10.60, P = .009), defensive backs (OR 12.20, CI 2.13-76.60, P = .006), linebackers (OR 8.98, CI 2.58-33.60, P < .001), more recent time of injury (OR 1.11, CI 1.05-1.17, P < .001), and shorter NFL experience (OR .77 for older athletes, CI .59-.99), P = .047) at significant risk for operative treatment. Conclusion: A total of 258 PM injuries were identified over 22 NFL seasons, with an overall incidence of 0.603 per 10,000 athlete-exposures, which was found to increase by 0.039 injuries per 10,000 athlete-exposures per year. Repair was performed in 48.8% of athletes, with more recent time of injury, shorter NFL experience, defensive linemen, defensive backs and linebackers at significantly higher risk for operative treatment.