A multi-layer circuit substrate and method having improved transmission line integrity and increased routing density uses a selectively applied transmission line reference plane metal layer to achieve signal path shielding and isolation, while avoiding drops in impedance due to capacitance between large diameter vias and the transmission line reference plane metal layer. The transmission line reference plane defines voids above (or below) the signal-bearing plated-through holes (PTHs) that pass through a rigid substrate core, so that the signals are not degraded by an impedance mismatch that would otherwise be caused by shunt capacitance from the top (or bottom) of the signal-bearing PTHs to the transmission line reference plane. For voltage-plane bearing PTHs, no voids are introduced, so that signal path conductors can be routed above or adjacent to the voltage-plane bearing PTHs, with the transmission line reference plane preventing shunt capacitance between the signal path conductors and the PTHs.