In 2017, the NCAA implemented rule changes to enhance safety in college football; however, the effect on injury risk remains unclear. The purpose of this study was to observe differences in the number and rate of injuries and time-loss injuries in an NCAA Division II football team during two consecutive preseasons, before and after the rule changes. From 2016 to 2017, we observed a decrease in lower extremity (LE) muscle strains from 1.00 injury/session to 0.55 injuries/session. We also observed a decrease in time-loss LE muscle strains from 0.52 injuries/session in 2016 to 0.20 injuries/session in 2017. After the rule changes, we observed fewer time-loss injuries (14.06% decrease), acute LE strains (45.00% decrease), and time-loss LE strains (61.54% decrease) per preseason practice session. These findings suggest that the rule changes may help reduce both the number and severity of LE muscle strains during preseason football.