The aims of this study were to examine the movement demands of preseason practice in National Collegiate Athletic Association Division I college football players using portable global positioning system (GPS) technology and to assess perceived wellness associated with preseason practice to determine whether GPS-derived variables from the preceding day influence perceived wellness the following day. Twenty-nine players were monitored using GPS receivers (Catapult Innovations, Melbourne, Australia) during 20 preseason practices. Individual observations (n = 550) were divided into offensive and defensive position groups. Movement variables including low-, medium-, high-intensity, and sprint distance, player load, and acceleration and deceleration distance were assessed. Perceived wellness ratings (n = 469) were examined using a questionnaire which assessed fatigue, soreness, sleep quality, sleep quantity, stress, and mood. A 1-way analysis of variance for positional movement demands and multilevel regressions for wellness measures were used, followed by post hoc testing to evaluate the relational significance between categorical outcomes of perceived wellness scores and movement variables. Results demonstrated significantly (p ≤ 0.05) greater total, high-intensity, and sprint distance, along with greater acceleration and deceleration distances for the defensive back and wide receiver position groups compared with their respective offensive and defensive counterparts. Significant (p ≤ 0.05) differences in movement variables were demonstrated for individuals who responded more or less favorably on each of the 6 factors of perceived wellness. Data from this study provide novel quantification of the position-specific physical demands and perceived wellness associated with college football preseason practice. Results support the use of position-specific training and individual monitoring of college football players.