A complex multiple-support response spectrum (CMSRS) method with a concise and universal expression is required to estimate the seismic responses of soil–structure interaction (SSI) systems under non-uniform seismic excitations to replace existing complex methods. This paper introduces and defines a new concept called equivalent acceleration of boundary load (EABL) that converts widely used equivalent loads into equivalent accelerations, and further develops an efficient CMSRS-EABL method for the seismic analysis of the SSI system. First, EABL offers three main benefits: it simplifies the expressions without sacrificing precision, extends the applicable scope of viscous-spring artificial boundary (VSAB) to all stress-type artificial boundaries, and presents dynamic equations in a familiar form. Subsequently, the CMSRS–EABL formula was successfully deduced based on the equivalent simplified dynamic equations. This formula significantly simplifies the traditional method by reducing the effective modal participation factors, mean-square-roots, and cross-correlation coefficients by 4, 5 and 15 items, respectively. Finally, a rectangular construction surrounded by a VSAB–soil combination was used as an example to illustrate the convenience of the developed CMSRS–EABL method and verify its precision. The results indicate that the proposed method is characterized by greater simplicity and ingenuity, and it is capable of high precision similar to that of the conventional methods. We believe this method will be of significant benefit in evaluating the anti-seismic performance of deeply buried and long-standing structures.