Background The Disabilities of the Arm, Shoulder and Hand (DASH) and Constant-Murley scores are commonly used instruments. The DASH is patient-reported, and the Constant-Murley combines a clinician-reported and a patient-reported part. For patients with a humeral shaft fracture, their validity, reliability, responsiveness, and minimal important change (MIC) have not been published. This study evaluated the measurement properties of these instruments in patients who sustained a humeral shaft fracture. Methods The DASH and Constant-Murley instruments were completed 5 times until 1 year after trauma. Pain score, Short Form 36, and EuroQol-5D were completed for comparison. Internal consistency was determined by the Cronbach α. Construct and longitudinal validity were evaluated by assessing hypotheses about expected Spearman rank correlations in scores and change scores, respectively, between patient-reported outcome measures (sub)scales. The smallest detectable change (SDC) was calculated. The MIC was determined using an anchor-based approach. The presence of floor and ceiling effects was determined. Results A total of 140 patients were included. Internal consistency was sufficient for DASH (Cronbach α = 0.96) but was insufficient for Constant-Murley (α = 0.61). Construct and longitudinal validity were sufficient for both patient-reported outcome measures (>75% of correlations hypothesized correctly). The MIC and SDC were 6.7 (95% confidence interval, 5.0-15.8) and 19.0 (standard error of measurement, 6.9), respectively, for DASH and 6.1 (95% CI −6.8 to 17.4) and 17.7 (standard error of measurement, 6.4), respectively, for Constant-Murley. Conclusions The DASH and Constant-Murley are valid instruments for evaluating outcome in patients with a humeral shaft fracture. Reliability was only shown for the DASH, making this the preferred instrument. The observed MIC and SDC values provide a basis for sample size calculations for future research.