In an ESD protection structure and method utilizing substrate triggering for a high-voltage tolerant pad on a substrate, an ESD protection device has a source connected to the pad and a gate and a drain both connected to a ground, and a substrate-triggering control circuit is used to keep the substrate at a low voltage during a normal operation, and pumping the substrate to a high voltage during an ESD event for the ESD protection device to be triggered much easier. The substrate-triggering control circuit is implemented with an active device, thereby reducing the chip size for the circuit and the loading effect on the pad.