In response to the rapid advances in microelectronics, novel cooling technologies are needed to meet increasing cooling requirements. As a paradigm-shifting technique, electrowetting-on-dielectric (EWOD) uses electric potential to control the movement of a liquid droplet on a dielectric surface. In this work, we developed an EWOD-based microfluidic technique for active and adaptive thermal management of on-chip hot spots. A two-dimensional array of control electrodes was patterned on the chip surface for EWOD operations. By applying DC or AC voltages with appropriate sequence and timing to the electrode units, we were able to transport microdroplets of tens of μL along a programmable path. Without the need of external pumps and valves, the droplets were precisely delivered to cooling targets. With the driving voltage as low as 40 VAC, we demonstrate high heat flux (7.6 W/cm2) cooling on a hot spot. The EWOD-induced internal circulation within the droplets led to a time-averaged Nusselt number of ̃45.