This brief presents a high efficiency fully integrated high-voltage (HV) pulse driver in standard CMOS. Powered by a standard I/O DC voltage of 2.5 V, the proposed system employs an optimized 4-stage cross-coupled switched-capacitor voltage multiplier (SCVM) together with an on-chip HV output driver to generate HV pulses of >10 V. We propose an area-efficient HV output driver stage to reach up to 12% total active area reduction when compared with the conventional implementation while maintaining the low static power characteristics. We also present a synchronous charge compensation (SQC) technique to alleviate the loading-dependent signal distortion through reducing the HV rail voltage droop and improving the HV pulse settling time during the driver output transitions. Fabricated in 65-nm bulk CMOS, the chip prototype can successfully generate HV pulses from 250 kHz to 1 MHz with a 15 pF load while ensuring no device breakdown. Measurement results demonstrate a peak SCVM power conversion efficiency (PCE) of 50% and an overall driving efficiency of 12.25%. The chip prototype attains a ∼ 2× faster output pulse transition speed compared with the state-of-the-art.