Knee injuries are among the most common musculoskeletal injuries in US football players. The literature includes little information about the role of player position and risk for knee injury. We hypothesized that the incidence of knee injury in elite collegiate US football players is high and that type of injury varies by player position. We evaluated 332 elite collegiate US football players at the 2005 National Football League Combine. All players underwent radiographic examinations, including plain x-rays and/or magnetic resonance imaging when necessary. All knee pathologic conditions and surgical procedures were recorded. Data were analyzed by player position to detect any trends. Fifty-four percent (179) of the 332 players had a history of knee injury; knee injuries totaled 233 (1.3/player injured). Eighty-six players (25.9%) had a total of 114 surgeries. The most common injuries were medial collateral ligament injury (n = 79), meniscal injury (n = 51), and anterior cruciate ligament (ACL) injury (n = 40). The most common surgeries were arthroscopic meniscectomy (n = 39), ACL reconstruction (n = 35), and arthroscopic meniscal repair (n = 13). A history of knee injury was most common in defensive linemen (68% of players), tight ends (57%), and offensive linemen (57%). Knee surgery was more commonly performed on running backs (36%) and linebackers (34%). There were no significant associations between type or frequency of specific injuries with regard to player position. Knee injuries are common injuries in elite collegiate football players, and one fourth of these players undergo surgical procedures. However, there were no statistically significant differences in type or frequency of injuries by player position.