An ultrasound (US) phased array with electronic steering and focusing capability can enable high-resolution, large-scale US interventions in various medical research and clinical experiments. For such applications involving different animal subjects and humans, the phased array system must provide flexibility in generating waveforms with different patterns (including experimental parameters), precise delay resolution between channels, and high voltage across US transducers to produce high US pressure output over extended durations. This paper presents a 16-channel high-voltage phased array system designed for therapeutic medical applications, capable of driving US transducers with pulses up to 100 V and a fine delay resolution of 5 ns, while providing a wide range of sonication waveforms. The modular 16-channel electronics are integrated with a custom-built, 2 MHz, 16-element US transducer array with dimensions of 4.3×11.7×0.7 mm³. In measurements, the phased array system achieved a peak-to-peak US pressure output of up to 6 MPa at a focal depth of 10 mm, with lateral and axial resolution of 0.6 mm and 4.67 mm, respectively. Additionally, the beam focusing and steering capability of the system in measurements and the theoretical analysis of the power consumption of the high-voltage driver (along with measured results) are provided. Finally, the phased array system’s ability to steer and focus the ultrasound beam for blood-brain barrier (BBB) opening in different brain regions is successfully demonstrated in vivo.