The purpose of this study was to investigate the relationship between overall physical workload (global positioning systems [GPS]/accelerometer) measures and injury risk in elite Australian football players (n = 46) during a season. Workload data and (intrinsic) injury incidence were monitored across preseason and in-season (18 matches) phases. Multiple regression was used to compare cumulative (1-, 2-, 3-, and 4-weekly loads) and absolute change (from previous-to-current week) in workloads between injured and uninjured players for all GPS/accelerometer-derived variables: total distance, V1 distance (total distance above individual's aerobic threshold speed), sprint distance, force load, velocity load, and relative velocity change. Odds ratios (ORs) were calculated to determine the relative injury risk. Cumulative loads showed the strongest relationship with greater intrinsic injury risk. During preseason, 3-weekly distance (OR = 5.489, p = 0.008) and 3-weekly sprint distance (OR = 3.667, p = 0.074) were most indicative of greater injury risk. During in-season, 3-weekly force load (OR = 2.530, p = 0.031) and 4-weekly relative velocity change (OR = 2.244, p = 0.035) were associated with greater injury risk. No differences in injury risk between years of Australian Football League system experience and GPS/accelerometer data were seen. From an injury risk (prevention) perspective, these findings support consideration of several GPS/accelerometer running load variables in Australian football players. In particular, cumulative weekly loads should be closely monitored, with 3-weekly loads most indicative of a greater injury risk across both seasonal phases. © 2014 National Strength and Conditioning Association.