The aim of the current study was to investigate the relationship between straight-sprint and change-of-direction performance. Total sprinting time and split time at 5 m were collected from 44 college football players during a 15-m straight sprint (SS15m) and a 15-m zigzag sprint with two 60° changes of direction (COD15m). Differences in sprinting time between COD15m and SS15m and between COD5m and SS5m were expressed as percentage of decrement at 5 m and 15 m (Δ%5m and Δ%15m). Significant and high correlations emerged between SS15m and COD15m (r = .86, P < .0001), SS5m and SS15m (r = .92, P < .0001), SS5m and COD5m (r = .92, P < .0001), and COD5m and COD15m (r = .71, P < .0001). Δ%5m and Δ%15m showed a range of 1.2–30.0% and 34.9–59.4%, respectively. These results suggested how straight-sprint and change-of-direction performance are similar abilities in college football players, in particular when a smaller angle of the change of direction is considered. Moreover, it seems necessary to have athletes undergo tests that mimic the demands of football game, which is characterized by sprint on short distances and with changes of direction.