Continuous pursuits for higher data rate, larger network capacity, low-latency communication, and better energy efficiency have motivated the development of the fifth generation (5 G) mobile communication technologies in recent years. Under a high-frequency transmission, the alternating electric current (AC) tends to distribute to the outer of a conductor due to the so-called “skin effect”; therefore, the surface coatings of Cu interconnect becomes an indispensable factor of the signal transmission characteristics. The focus of this study is to deeply probe into the effect of surface coatings on the high-frequency signal transmission (1–100 GHz) of Cu interconnects. We investigated six different surface finishes over a coplanar waveguide (CPW) transmission line structure, including immersion tin (ImSn), immersion silver (ImAg), immersion gold (IG), electroless palladium/immersion gold (EPIG), immersion gold/electroless palladium/immersion gold (IGEPIG), and ultrathin-Ni(P)-type ENEPIG. The high-frequency signal performance of the CPW transmission line was analyzed through the finite element analysis (FEA) method by using a 3D electromagnetic simulation software. Furthermore, experimental measurements were conducted by using a vector network analyzer (VNA) to characterize the signal loss arising from different surface finishes, so as to validate the numerical simulation results. The FEA and VNA results showed that a noticeable current redistribution might be induced by a high conductivity/permeability of surface coating(s), i.e., ImSn and ultrathin-Ni(P)-type ENEPIG, which significantly increases the signal insertion loss at high frequencies. Thus, an appropriate surface coating over Cu interconnects was necessary for enhancing the high-frequency signal transmission performance.