An area-efficient, high voltage, single polarity ESD protection device (300) is provided which includes an p-type substrate (303); a first p-well (308-1) formed in the substrate and sized to contain n+ and p+ contact regions (310, 312) that are connected to a cathode terminal; a second, separate p-well (308-2) formed in the substrate and sized to contain only a p+ contact region (311) that is connected to an anode terminal; and an electrically floating n-type isolation structure (304, 306, 307-2) formed in the substrate to surround and separate the first and second semiconductor regions. When a positive voltage exceeding a triggering voltage level is applied to the cathode and anode terminals, the ESD protection device triggers an inherent thyristor into a snap-back mode to provide a low impedance path through the structure for discharging the ESD current.