Background: Physical activity reduces the incidences of noncommunicable diseases, obesity, and mortality, but an inactive lifestyle is becoming increasingly common. Innovative approaches to monitor and promote physical activity are warranted. While individual monitoring of physical activity aids in the design of effective interventions to enhance physical activity, a basic prerequisite is that the monitoring devices exhibit high validity. Objective: Our goal was to assess the validity of monitoring heart rate (HR) and energy expenditure (EE) while sitting or performing light-to-vigorous physical activity with 4 popular wrist-worn wearables (Apple Watch Series 4, Polar Vantage V, Garmin Fenix 5, and Fitbit Versa). Methods: While wearing the 4 different wearables, 25 individuals performed 5 minutes each of sitting, walking, and running at different velocities (ie, 1.1 m/s, 1.9 m/s, 2.7 m/s, 3.6 m/s, and 4.1 m/s), as well as intermittent sprints. HR and EE were compared to common criterion measures: Polar-H7 chest belt for HR and indirect calorimetry for EE. Results: While monitoring HR at different exercise intensities, the standardized typical errors of the estimates were 0.09-0.62, 0.13-0.88, 0.62-1.24, and 0.47-1.94 for the Apple Watch Series 4, Polar Vantage V, Garmin Fenix 5, and Fitbit Versa, respectively. Depending on exercise intensity, the corresponding coefficients of variation were 0.9%-4.3%, 2.2%-6.7%, 2.9%-9.2%, and 4.1%-19.1%, respectively, for the 4 wearables. While monitoring EE at different exercise intensities, the standardized typical errors of the estimates were 0.34-1.84, 0.32-1.33, 0.46-4.86, and 0.41-1.65 for the Apple Watch Series 4, Polar Vantage V, Garmin Fenix 5, and Fitbit Versa, respectively. Depending on exercise intensity, the corresponding coefficients of variation were 13.5%-27.1%, 16.3%-28.0%, 15.9%-34.5%, and 8.0%-32.3%, respectively. Conclusions: The Apple Watch Series 4 provides the highest validity (ie, smallest error rates) when measuring HR while sitting or performing light-to-vigorous physical activity, followed by the Polar Vantage V, Garmin Fenix 5, and Fitbit Versa, in that order. The Apple Watch Series 4 and Polar Vantage V are suitable for valid HR measurements at the intensities tested, but HR data provided by the Garmin Fenix 5 and Fitbit Versa should be interpreted with caution due to higher error rates at certain intensities. None of the 4 wrist-worn wearables should be employed to monitor EE at the intensities and durations tested.