Few studies have explored the frequency and impact of lower extremity injuries, such as those to the knee, among professional baseball players. The purpose of this study was to detail the epidemiology of knee injuries in Major League Baseball (MLB) and Minor League Baseball (MiLB) players during the 2011-2014 seasons. It was hypothesized that knee injuries are a common occurrence in these athletes, and represent a significant source of time away from play. The MLB Health and Injury Tracking System database was searched to identify all patients diagnosed with knee injuries during the 2011-2014 seasons. All injuries that occurred during the preseason, regular season, and postseason that resulted in time away from play were included. Injury data analyzed included total number of knee injuries, specific diagnoses, injury mechanisms, locations, player positions, and time lost. Descriptive statistics were conducted and injury rates per athlete-exposures were calculated. During the 2011-2014 seasons, a total of 2171 knee injuries occurred in MLB and MiLB players, representing 6.5% of all injuries in professional baseball. The knee injury rate across both the MLB and MiLB was 1.2 per 1000 athlete-exposures. The mean number of days missed per injury across both leagues was 16.2 with a total of 30,449 days of missed play amongst all athletes over the 4 seasons. Injuries to the knee were the fifth most common cause of missed time in all of baseball, and the fourth most common reason for missed games in the MLB alone. Approximately 12% of all injuries required surgical intervention. The most common mechanism of injury was noncontact (44%), and base runners were injured more frequently than any other position (24%). The infield (30%) and home plate (23%) were the most common locations in which injuries occurred. These data can be utilized for targeted injury prevention initiatives.