The purpose of this paper is to demonstrate a prototype design of a low-frequency multiple-channel hemispherical focused-ultrasound phased-array system for transcranial disruption of the blood-brain barrier (BBB). A 32-channel ultrasound driving system tunable in the frequency range from 200 to 400 kHz was designed for producing a suitable ultrasound output for BBB disruption. The driving system includes a microcontroller/field-programmable gate-array-based control kernel with multiple-channel driving circuits implemented by a high-voltage switching/LC-resonance/impedance-matching circuit module. Three hemispherical phased arrays comprising 22, 31, and 80 elements were fabricated and tested. The pressure distributions at the geometric center and at off-center positions were tested experimentally. The focal performance of the different hemispherical arrays was also evaluated theoretically. The results showed that the developed phased-array system can successfully drive the hemispherical array with multiple-channel ultrasound signals with independent phase control at 8-bit resolution. Good focusing abilities were evident both at the geometric center and at specific off-center target positions. Preliminary animal experiments show that the BBB in rat can be locally disrupted successfully. The system will serve as a reference platform for developing a focused-ultrasound system for clinical use in brain drug delivery applications.