In this paper, efficiency-limiting physical constraint effects imposed on the knee voltage, along with a variation of the optimum load resistance, are investigated for highly efficient Class-F and Class- amplifiers. First, for an accurate analysis and comparison, new current waveform models are identified, and a realistic approach incorporated using a nonzero knee voltage and voltage-dependent nonlinear capacitance is employed to derive the voltage waveforms of the amplifiers. An analysis is performed to show the efficiency, output power, power gain, and output power compression points for both modes. Using this knowledge, along with a complete performance comparison, we provide a direction for optimizing the amplifier design. The analytic results are further verified based on the measured results of 3.54-GHz Class-F and Class- amplifiers using a commercial 60-W peak-to-envelope power gallium-nitride device. The experimental results show that Class-F and Class- amplifiers operate at drain efficiencies of 69.9% and 69.4% at saturated output powers of 47.4 and 47.2 dBm, respectively. These remarkably similar performances have excellent agreement with the predicted analysis at our operational frequency.