A ESD protection scheme is disclosed for circuits with multiple power domains. Embodiments include: coupling a first power clamp to a first power rail and a first ground rail of a first domain; coupling a second power clamp to a second power rail and a second ground rail of a second domain; providing a blocking circuit for blocking current from an ESD event; providing an I/O interface connection in the first domain for transmitting signals from the first domain to the blocking circuit; providing a core interface connection in the second domain for transmitting signals from the blocking circuit to the second domain; coupling an input connection of the blocking circuit to the I/O interface connection; and coupling an output connection of the blocking circuit to a core interface connection.