An electrostatic discharge protection circuit that includes at least two transistors connected in a stacked configuration, a first diffusion region of a first dopant type shared by two adjacent transistors, and a second diffusion region of a second dopant type formed in the first diffusion region. A substrate-triggered site is induced into the device structure of the stacked transistors to improve ESD robustness and turn-on speed. An area-efficient layout to realize the stacked transistors is proposed. The stacked transistors may be implemented in ESD protection circuits with a mixed-voltage I/O interface, or in integrated circuits with multiple power supplies. The stacked transistors are fabricated without using a thick-gate mask.