Several embodiments of electrical circuit devices and systems with clock distortion calibration circuitry are disclosed herein. In one embodiment, an electrical circuit device includes clock distortion calibration circuitry to calibrate a clock signal. The clock distortion calibration circuitry is configured to determine when one or more duty cycle calibration (DCC) conditions are met. When the DCC condition(s) are met, the clock distortion calibration circuitry is configured adjust a trim value associated with at least one of first and second duty cycles of first and second voltage signals, respectively. In some embodiments, the clock distortion calibration circuitry is configured to calibrate at least one of the first and the second duty cycles of the first and the second voltage signals using the adjusted trim value to account for duty cycle distortion encountered across various voltages and/or temperatures while the electrical circuit devices and/or systems remain in a powered on state.