Current testing of small-arms weapons focuses on measuring accuracy in optimal, supported positions whereas using a more dynamic test may be more informative. Previous work has shown that accuracy, shot interval, and weapon stability degrades over prolonged shooting and only the latter two measures differ between weapon configurations. The aim of the current study was to evaluate muscle activity to understand if signs of fatigue could add information about the optimal ergonomic weapon. The 200 ms of electromyography from six upper limb muscles immediately before each of 60 shots for four weapon conditions were collected from 18 participants. Both frequency and amplitude showed signs of muscle fatigue over the 60 shots for most of the muscles, and amplitude was different in some muscles between conditions. This study shows that although participants can maintain accuracy with more difficult weapon configurations, this comes at the potential cost of muscle fatigue.