Objective: The effects of diverse periodic interventions on trapezius muscle fatigue and activity during a full day of computer work were investigated. Background: Musculoskeletal disorders, including trapezius myalgia, may be associated with repeated exposure to prolonged low-level activity, even during light upper-extremity tasks including computer work. Methods: Thirty healthy adults participated in a study that simulated two 6-hour workdays of computer work. One workday involved imposed periodic passive and active interventions aimed at disrupting trapezius contraction monotony (Intervention day), whereas the other workday did not (Control day). Trapezius muscle activity was quantified by the 3-dimensional acceleration of the jolt movement of the acromion produced by electrically induced muscle twitches. The spatio-temporal distribution of trapezius activity was measured through high-density surface electromyography (HD-EMG). Results: The twitch acceleration magnitude in one direction was significantly different across measurement periods (p = 0.0156) on Control day, whereas no significant differences in any direction were observed (p > 0.05) on Intervention day. The HD-EMG from Intervention day showed that only significant voluntary muscle contractions (swing arms, Jacobson maneuver) induced a decrease in the muscle activation time and an increase in the spatial muscle activation areas (p < 0.01). Conclusion: Disruption of trapezius monotonous activity via brief voluntary contractions effectively modified the ensuing contraction pattern (twitch acceleration along one axis, active epochs reduction, and larger spatial distribution). The observed changes support an associated reduction of muscle fatigue. Application: This study suggests that disruptive intervention activity is efficient in reducing the impact of trapezius muscle fatigue.