Purpose: The purpose of this study was to determine magnitudes of differences for anthropometric and athletic performance scores between high school and elite college-level American football players. Method: Participants included high school-age (n = 3,666) athletes who participated in American football combines, as well as elite college-level (n = 5,537) athletes who participated in the National Football League (NFL) scouting combine. Combine data included position; height; weight; 10-, 20-, and 40-yard dash; pro-agility (PA); L-cone drill (LC); vertical jump (VJ); and broad jump (BJ). Athletes were separated into their respective position group, defensive back (DB), wide receiver (WR), linebacker (LB), quarterback (QB), running back (RB), tight end (TE), defensive line (DL), and offensive line (OL) for analysis of performance differences. Percent differences for each dependent variable were calculated to quantify magnitudes of differences. Results: NFL combine participants scored 3% to 25% better on all measurements, with the largest differences between weight and VJ (14%-25%). Conclusion: The largest measurement-specific differences between high school-age and elite college-level American football players were body size and power. Although it may seem intuitive that elite college-level players would perform better, these data provide a unique perspective to high school players, parents, and coaches, giving new information to use when designing measurement-specific athletic development programs. Thus, strength and conditioning professionals may benefit from emphasizing increases in muscle mass and power output in strength and conditioning programs.